Esophageal Cancer Cell Line Eca-109 Research Articles

Synthesis and evaluation of new tetrapyrrole derivatives with photodynamic anti-tumor effects

As a promising anti-tumor method, photodynamic therapy (PDT) has garnered increased interest over the past decades. Since the efficacy of PDT relies on the properties of photosensitizers, tremendous efforts have been exerted in the quest for novel photoactive agents with long wavelength absorbance and high phototoxicity. In this investigation, a series of five tetrapyrrole derivatives were newly synthesized and evaluated. They all manifested sharp UV–vis absorption peak at ∼680 nm, high molar extinction coefficient (>74200 L mol−1 cm−1), impressive reactive oxygen species generation abilities and obvious photo-damage on cancer in vitro and in vivo. Among them, I4 displayed the most excellent singlet oxygen generation slope (K = 0.0531 s−1, ΦΔ = 0.87), the strongest anti-proliferation effects towards human esophageal cancer cell line Eca-109 in vitro, and more remarkable tumor inhibition rates (90.2 %) than m-THPC in vivo. Subcellular localization experiments demonstrated that I4 could distribute in mitochondria, endoplasmic reticulum and lysosomes. Hence, compound I4 could be viewed as a potential photosensitizer drug for further studies in PDT.

Inhibition of p62-Keap1-Nrf2 Pathway Activation by Realgar Promotes the Inhibition of Esophageal Cancer Cell Proliferation, Migration, and Ferroptosis.

Realgar, a Chinese herbal decoction, has been used to treat various types of tumors with positive outcomes; however, there is a lack of convincing evidence on its use for the treatment of esophageal cancer (EC). In this study, the role of the p62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in the regulation of EC cell proliferation, migration, and ferroptosis in response to realgar was assessed. Different concentrations of realgar (0, 10, 20, 40, 60, 80, and 100 μmol/L) were applied to the EC cell lines Eca109 and KYSE150. The inhibition rate and half-inhibitory concentration (IC50) were determined using the Cell Counting Kit-8 (CCK-8) method. Subsequently, the cells were treated with realgar (1/2IC50, IC50, 2IC50). Cell migration was measured using the scratch assay, and cell invasion was measured using the transwell assay. The mRNA expression of p62, Keap1, and Nrf2 was measured by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression of p62, Keap1, Nrf2, matrix metalloproteinase (MMP)-2, MMP-9, E-cadherin, Slug, N-cadherin, and vimentin was measured by Western blot. The control, 2IC50, shRNA-NC, shRNA-p62, 2IC50 + shRNA-NC, 2IC50 + shRNA-p62, shRNA-Keap1, 2IC50 + shRNA-Keap1, and 2IC50 + shRNA-p62 + shRNA-Keap1 groups were defined. The CCK-8 method was used to measure the cell inhibition rate, and the clone formation assay was used to measure the clone formation ability. Moreover, the scratch assay was used to detect the cell migration ability, and the transwell assay was used to detect the cell invasion ability. Transmission electron microscopy was used to observe the mitochondrial morphology, Prussian blue staining was used to observe the intracellular iron particle distribution, and flow cytometry was used to detect changes in intracellular reactive oxygen species. In addition, qRT-PCR was performed to detect p62, Keap1, Nrf2, and glutathione peroxidase 4 (GPX4) mRNA expression, and Western blot was performed to detect p62, Keap1, Nrf2, E-cadherin, Slug, N-cadherin, and GPX4 protein expression. Realgar inhibited Eca109 and KYSE150 cell proliferation in a time- and concentrationdependent manner. It also significantly inhibited the migration and invasion of Eca109 and KYSE150 cells and affected the mRNA and protein expression of p62, Keap1, and Nrf2. In response to realgar, low p62 expression inhibited the proliferation, migration, and invasion of Eca109 and KYSE150 cells, as well as ferroptosis induction. The findings demonstrate that inhibiting the p62-Keap1-Nrf2 signaling pathway promotes the inhibitory effects of realgar on EC cells.

Synthesis, characterization, antiproliferative activity and DNA binding calculation of substituted-phenyl-terpyridine copper(II) nitrate complexes

Ten 4′- (R-phenyl) -2,2′: 6′, 2′ – terpyridine ligands (R = hydrogen (L1), hydroxyl (L2), methoxyl (L3), methylsulfonyl (L4), methyl (L5), phenyl (L6), fluoro (L7), chloro (L8), bromo (L9), and iodo (L10)) were synthesized. The reaction of these ligands with copper(II) nitrate led to complexes 1–10. The characterization of 1–10 was carried out by means of mass spectrometry, elemental analysis, infrared spectroscopy and X-ray single crystal diffraction. Four cell lines including esophageal cancer cell line (Eca-109), human liver cancer cell line (Bel-7402), human breast cancer cell line (SIHa) and human normal liver cell line (HL-7702) were selected to carry out antiproliferation and cytotoxicity experiments in vitro. The results showed that the complexes have strong inhibitory ability on the growth of tumor cells. In order to study the anticancer mechanism of the complexes, the binding mode and binding ability of the complexes with DNA were further determined and discussed with UV–Vis spectroscopy and circular dichroism. The effects of the lowest binding energy and hydrogen bond on the binding were studied using molecular docking calculation.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

Nickel chloride complexes with substituted 4'-phenyl-2',2':6',2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions.

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4'-(4-substituent phenyl)-2',2':6',2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI-MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC50 values of 0.223μM and 0.335μM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

Ophiopogon Japonicus Polysaccharide Plays an Anti-esophageal Cancer Role Through Antioxidant Activity

As a natural product with a variety of biological activities, plant polysaccharide has become a research highlight in the field of antioxidant activity and anti-tumor due to its high efficiency and low toxicity. In this study, the antioxidant and anti-tumor activities of Ophiopogon japonicus polysaccharides (OJP) in vitro and in vivo were investigated. The results showed that OJP had obvious scavenging ability on hydroxyl radical and superoxide radical in a dose-dependent manner. Moreover, the reducing power of OJP also increased and appeared to be dose-dependent. In vivo, it reduced the accumulation of lipofuscin and induced cell apoptosis of Caenorhabditis elegans. In addition, it significantly inhibits the viability of esophageal cancer cell lines Eca109 and TE-1 in vitro and promoted their apoptosis. In conclusion, OJP avoids oxidative damage of organisms and plays an anti-tumor role via its antioxidation. This study aims to promote the in-depth study of plant polysaccharides and provide theoretical reference for the development of antioxidant foods and anti-tumor drugs.

Fe(II) complexes of 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups: synthesis, crystal structures and anticancer potential.

With the aim of developing potential anticancer drug candidates, a series of Fe(II) complexes were synthesized using nine 2,2':6',2''-terpyridine ligands functionalized with substituted-phenyl groups, and their biological activities were systematically investigated. Their bis-terpyridine sandwich-like structures were determined by single crystal X-ray crystallography. In vitro antiproliferative experiments based on three human cancer cell lines, including human hepatoma cancer cell line (Bel-7402), human esophageal cancer cell line (Eca-109), and human cervical squamous cancer cell line (SiHa), indicate the high antiproliferation activities of these complexes compared with commercial cisplatin. And their toxicity to normal cells was estimated based on human normal hepatocyte (HL-7702) cell line. In particular, when the phenyl in terpyridine ligand was modified by a carboxyl group, the corresponding complex 3 exhibited much higher antiproliferation to cancer Bel-7402 cells (IC50 = 3.653 μmol L-1) than cisplatin and low toxicity to normal HL-7702 cells (IC50 = 99.92 μmol L-1), implying a significant selectivity for 3 in killing hepatoma cancer cells. Combined with the fact that iron element is more accessible than platin, this series of Fe(II) complexes comprises potential candidates for anticancer drugs with specific inhibition of hepatoma cancer. UV titration experiments and circular dichroism (CD) showed a strong binding affinity between these nine complexes and CT-DNA. However, molecular docking simulation revealed the competitive binding of DNA and protein to these complexes. Further, the interactions between these complexes and bovine serum albumin (BSA) have been studied by fluorescence titration and CD spectroscopy.

Essential oil from Saussurea costus inhibits proliferation and migration of Eca109 cells via mitochondrial apoptosis and STAT3 signaling

Objective: To investigate the effect and its underlying molecular mechanisms of essential oil from Saussurea costus in esophageal cancer cell line Eca109. Methods: The chemical composition of essential oil from Saussurea costus was investigated by gas chromatography-mass spectrometry (GC-MS). The anti-proliferative, anti-migrative, and apoptotic effects of essential oil from Saussurea costus against Eca109 cells were analyzed. Moreover, the expression of proteins associated with cell cycle, metastasis, and apoptosis was determined. Results: GC-MS analysis showed that essential oil from Saussurea costus was predominantly comprised of sesquiterpenes. Saussurea costus essential oil inhibited the viability of Eca109 cells in a dose-and time-dependent manner with IC50 values of (24.29±1.49), (19.16±2.27) and (6.97±0.86) μg/mL at 12, 24, and 48 h, respectively. The expression levels of target proteins in the cell cycle (phase G1/S), including cyclin D1, p21, and p53, were affected by Saussurea costus essential oil. The essential oil also downregulated the expression of metastasis-related proteins MMP-9 and MMP-2. Moreover, it induced apoptosis of Eca109 cells through the mitochondrial pathway, as well as inhibition of STAT3 phosphorylation. Conclusions: The essential oil from Saussurea costus exhibited anti-proliferative, anti-migrative, and apoptotic effects on Eca109 cells, and could be further explored as a potential anti-esophageal cancer agent.

Human Telomerase Reverse Transcriptase as a Therapeutic Target of Dihydroartemisinin for Esophageal Squamous Cancer

Objective: To elucidate the oncogenic role of human telomerase reverse transcriptase (hTERT) in esophageal squamous cancer and unravel the therapeutic role and molecular mechanism of dihydroartemisinin (DHA) by targeting hTERT. Methods: The expression of hTERT in esophageal squamous cancer and the patients prognosis were analyzed by bioinformatic analysis from TCGA database, and further validated with esophageal squamous cancer tissues in our cohort. The Cell Counting Kit-8 (CCK8) and colony formation assay were used to evaluate the proliferation of esophageal squamous cancer cell lines (Eca109, KYSE150, and TE1) after hTERT overexpression or treated with indicated concentrations of DHA. Transwell migration assay and scratch assay were employed to determine the migration abilities of cancer cells. Fluorescence microscopy and flow cytometry were conducted to measure the intracellular reactive oxygen species (ROS) levels in cancer cells after treated with DHA. Moreover, RT-PCR and Western blot were performed to test the alteration of associated genes on mRNA and protein level in DHA treated esophageal squamous cancer cell lines, respectively. Furthermore, tumor-bearing nude mice were employed to evaluate the anticancer effect of DHA in vivo. Results: We found that hTERT was significantly upregulated in esophageal squamous cancer both from TCGA database and our cohort also. Overexpression of hTERT evidently promoted the proliferation and migration of esophageal squamous cancer cells in vitro. Moreover, DHA could significantly inhibit the proliferation and migration of esophageal cancer cell lines Eca109, KYSE150, and TE1 in vitro, and significantly down-regulate the expression of hTERT on both mRNA and protein level in a time- and dose-dependent manner as well. Further studies showed that DHA could induce intracellular ROS production in esophageal cancer cells and down-regulate SP1 expression, a transcription factor that bound to the promoter region of hTERT gene. Moreover, overexpression of SP1 evidently promoted the proliferation and migration of Eca109 and TE1 cells. Intriguingly, rescue experiments showed that inhibiting ROS by NAC alleviated the downregulation of SP1 and hTERT in cells treated with DHA. Furthermore, overexpression of SP1 or hTERT could attenuate the inhibition effect of DHA on the proliferation and migration of Eca109 cells. In tumor-bearing nude mice model, DHA significantly inhibited the growth of esophageal squamous cancer xenografts, and downregulated the expression of SP1 and hTERT protein, while no side effects were observed from heart, kidney, liver, and lung tissues by HE stain. Conclusion: hTERT plays an oncogenic role in esophageal squamous cancer and might be a therapeutic target of DHA through regulating ROS/SP1 pathway.

Folic Acid Inhibited Vasculogenic Mimicry in Esophageal Cancer Cell Line Eca-109, the One Target Was EphA2

The degree of vasculogenic mimicry(VM) is correlated with the prognosis of esophageal cancer, and folic acid supplementation could decrease esophagus cancer deaths among populations. This study aimed to explore the effect of folic acid on VM formation of esophageal cancer cell, and the target. Human esophageal squamous cancer cell lines(Eca-109) were cultured with different concentrations of folic acid (0,1,10,100,200,400, 600,800 μg/ml). A cell counting kit-8 (CCK-8) assay was used to measure the cell proliferation. Then, the amount of VM under the effect of different concentrations of folic acid was observed. Target genes were screened out from several possible targets genes including MMP2, MMP9, EphA2, VE-cad or Ln-5γ2 by employing reverse transcription-quantitative polymerase chain reaction(RT-qPCR). Finally, western blot analysis was used to verify the target proteins. In conclusion, this study found that folic acid inhibited the formation of VM in Eca-109 cells, and the one target protein was EphA2.

Incorporation of green emission polymer dots into pyropheophorbide-α enhance the PDT effect and biocompatibility

BackgroundA green emission up-conversion carbon-based polymer dots (CPDs) owned excellent photophysical properties and good solubility. Most photosensitizers (PS) are hydrophobic which limits their application in biomedicine. Herein we synthesized and integrated green emitting CPDs into pyropheophorbide-α (PPa) to improve the overall properties of the PS. Material and methodsThe nano-agent was incorporated through amide condensation and electrostatic interaction. The structure, size and morphology of the prepared conjugates were determined by FTIR, TEM, DLS, TGA, 1HNMR, Uv-vis, and fluorescence spectrophotometry. The dark and light toxicity, as well as cellular uptake, was also monitored on the human esophageal cancer cell line (Eca-109). ResultsOur results illustrate that the conjugation improved the PDT efficacy by increasing the ROS generation. The nano-hybrids showed pH sensitivity as well as good hemocompatibility as the hemolysis ratio was decreased when treated with nano-conjugates. PPa-CPD1 and PPa-CPD2 had the pH response and stronger ability to absorb light and produce fluorescence in an acidic environment (pH 4.0 and pH 5.0) The synthesized nano-hybrids doesnot affect the clotting time. An increase in the absorbance wavelengths was observed. The results of MTT assay showed that dark toxicity was reduced after conjugation. ConclusionThis CPDs-based drug enhanced tumor-inhibition efficiency as well as low dark toxicity in vitro, showing significant application potential for PDT-based treatment.

Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

Esophageal cancer is a common tumor of the digestive system with poor prognosis. This study was to gain a better understanding of the mechanisms involved in esophageal cancer and to identify new prognostic markers. We downloaded the esophageal cancer miRNA expression profile microarray data (GSE113740, GSE112264, GSE122497, GSE113486, and GSE106817) from the GEO database, extracted the esophageal cancer miRNA sequencing data from The Cancer Genome Atlas (TCGA) database, and then used a bioinformatics approach to select common differentially expressed miRNAs (DEMs). Differentially expressed genes (DEGs) were selected by predicting DEM target genes using the miRWalk database and intersecting with differential genes obtained from TCGA database for esophageal cancer. The STRING database was used to obtain protein–protein interaction (PPI) relationships to construct the DEM-DEG network. Furthermore, we selected core genes and core miRNAs associated with esophageal cancer prognosis by performing survival and univariate/multivariate COX analysis on DEMs and DEGs in the network and performed GSEA analysis on core genes alone, and finally the expression of the markers was verified by qPCR in esophageal cancer cell lines Eca109, SKGT-4 and normal esophageal epithelial cells HEEC. Nine DEMs were obtained, of which three were upregulated and six were downregulated, and 326 DEGs were obtained, of which 105 were upregulated and 221 were downregulated. Survival univariate/multivariate COX analysis revealed that five genes, ZBTB16, AQP4, ADCYAP1R1, PDGFD, and VIPR2, and two microRNAs, miR-99a-5p, and miR-508-5p, were related to esophageal cancer prognosis. GSEA analysis showed that the following genes may be involved in esophageal cancer prognosis: ZBTB16 may through the MTOR signaling pathway, AQP4 through the GNRH signaling pathway, ADCYAP1R1 through the PPAR signaling pathway, VIPR2 through the P53 signaling pathway and PDGFD through the PENTOSE-PHOSPHATE signaling pathway.

Poly(A)-Specific Ribonuclease (PARN) Promotes the Proliferation, Migration and Metastasis of Esophageal Cancer

Background: Esophageal cancer leads to the majority of cancer deaths in the world. Surgery, radiotherapy and chemotherapy are the main treatment methods, but due to its high recurrence and metastasis rate, the overall prognosis is poor. Poly(A)-specific ribonuclease (PARN) is a multifunctional enzyme molecule, which is involved in the occurrence and development of tumors. This study explores the relationship between PARN and the proliferation, metastasis and prognosis of esophageal cancer. Methods: The esophageal cancer tissues and adjacent normal tissues were collected from 91 patients with esophageal cancer after surgery. The expression level of PARN was detected by immunohistochemistry (IHC) using tissue microarray (TMA). PARN expression and its relationships with clinicopathological characteristics and prognosis was detected. In addition, stable PARN knockdown esophageal cancer cell lines TE-1 and Eca-109 were used to study its effect on the phenotype and behavior of tumor cells. Meanwhile, the effect of PARN silencing on tumor growth in vivo was verified by xenotransplantation model in nude mice. Finally, we examined possible downstream signaling mechanisms of PARN in esophageal cancer. Findings: PARN showed high expression in esophageal carcinoma tissues and its expression was significantly correlated with lymphatic metastasis and prognosis of patients. In the culture of PARN knockdown esophageal cancer cell lines, the growth and proliferation were significantly inhibited, and the invasion and migration ability of tumor cells were also significantly decreased. In addition, inhibition of PARN suppressed tumor growth and increased survival time in xenograft murine models. In the PARN knockdown group, BIM, IGFBP-5 and p21 were significantly increased, while the expression levels of anti-apoptotic proteins Survivin and STNF-R1 were significantly down-regulated. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 downstream of the signaling pathway regulating esophageal cancer progression were significantly down-regulated. Interpretation: These results suggest a previously undetected role of PARN as a suppressor of tumor development and its associations of prognosis in esophageal cancer through anti-apoptotic effect. Funding Information: None. Declaration of Interests: The authors declare no conflicts of interests. Ethics Approval Statement: Ethical approval for the study was approved by the Research Ethics Committee of the Second Affiliated Hospital of Guangxi Medical University and Zhujiang Hospital Affiliated to Southern Medical University, and written patient consent was obtained from all patients. Nude mice xenograft model - This study was approved by the Guangxi Medical University Ethics Committee.

Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis.

Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.

The Photodynamic Anti-Tumor Effects of New PPa-CDs Conjugate with pH Sensitivity and Improved Biocompatibility.

Photodynamic therapy has been increasingly used to cope with the alarming problem of cancer. Porphyrins and their derivatives are widely used as Potent Photosensitizers (PS) for PDT. However, the hydrophobicity of porphyrins poses a challenge for their use in clinics, while most of the carbon dots (CDs) are known for good biocompatibility, solubility, and pH sensitivity. This study aimed to improve the properties/biocompatibility of the pyropheophorbide-α for PDT. The PPa-CD conjugate was synthesized through covalent interaction using amide condensation. The structure of synthesized conjugate was confirmed by TEM, 1HNMR, and FTIR. The absorption and emission spectra were studied. In vitro, cytotoxicity of the conjugate was examined in human esophageal cancer cell line (Eca-109). The results showed that the fluorescence of the drug was increased compared to its precursor. CDbased conjugate could generate ROS as well as enhanced biocompatibility by decreasing cytotoxicity. The conjugated drug also showed pH sensitivity in different solutions. The dark toxicity, as well as hemocompatibility, was improved.

Synthesis and in vitro PDT evaluation of red emission polymer dots (R-CPDs) and pyropheophorbide-\u03b1 conjugates

Carbon based polymer dots have piqued attention of researchers because of excellent biocompatibility, and good solubility. Most of the p-dots are able to generate ROS which is effective for photodynamic therapy for the treatment of cancer while some photosensitizers such as porphyrins possess some drawbacks such as hydrophobicity, and dark toxicity. Therefore in this study we conjugated red emission carbon based polymer with pyropheophorbide-α through amide condensation and π–π stacking. One pot synthesis of the conjugate was successfully achieved. Their photophysiological properties were studied and structures were characterized by FT-IR, TEM and 1HNMR. pH- sensitivity of the conjugates was confirmed using fluorescence and UV–vis spectroscopy. Photo toxicity and dark toxicity of the prepared conjugates were evaluated in human esophageal cancer cell line (Eca-109). Hemocompatibility of the synthesized conjugates was evaluated and proved that the conjugates are safe to use for the treatment of tumor. Our results showed the PS doped p-dots had less dark toxicity and increased light toxicity as well as ROS generation was high as compared to precursor drug. Therefore, incorporation of p-dots to porphyrin improved biocompatibility and enhanced the photodynamic effect.

Quercetin inhibits invasion and angiogenesis of esophageal cancer cells

BackgroundEsophageal carcinoma has poor prognosis and novel therapies for esophageal carcinoma are urgently needed. Quercetin is a natural flavonoid compound that can be found in many foods. In this study, we investigated the effects of quercetin on invasion and angiogenesis of esophageal cancer cells. MethodsHuman esophageal cancer cell line Eca109 was treated with 5 μg/mL or 10 μg/mL of quercetin. Colony formation assay was performed. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. Human umbilical vein/vascular endothelium cells (CLR-1730) were treated with Eca109 conditioned medium, and the effects of quercetin on CLR-1730 were evaluated by wound healing and tube formation assays. Protein levels of VEGF-A, MMP9, and MMP2 were determined by Western blotting. ResultsThe ability of colony forming in Eca109 was reduced with the administration of 10 μg/mL quercetin, but there was no difference between the 5 μg/mL quercetin group and control. The migration distance and the number of invasive cells were significantly reduced in the 10 μg/mL quercetin group. At the lower level of quercetin at 5 μg/mL, only the invasion of cells was significantly inhibited. In endothelial cells treated with Eca109 conditioned medium, cell migration and tube forming ability were suppressed. The decreased protein levels of VEGF-A, MMP9, and MMP2 were observed at the 10 μg/mL quercetin group. ConclusionQuercetin suppressed the invasion and angiogenesis of esophageal cancer cells, and the effects were associated with the decreased expression of VEGF-A, MMP2, and MMP9.

Circular RNA BMI1 Serves as a Potential Target for Diagnosis and Treatment in Esophageal Cancer.

Aims:Previous studies have confirmed that BMI1 is elevated in esophageal cancer, which is a potential therapeutic target for esophageal cancer. However, the clinical significance of circular RNA BMI1 (circ-BMI1) in esophageal cancer is not yet clear. Herein, we revealed the clinical implication of circ-BMI1 in esophageal cancer, and provided a theoretical basis for molecular diagnosis and potential targeted therapy of esophageal cancer.Methods:Firstly, 10 fresh paired esophageal cancer tissues and paracancer tissues, 49 esophageal cancer serum samples and 28 healthy control serum samples were involved in our study. Differential expression and clinical significance of circ-BMI1 in esophageal cancer patients and healthy controls were evaluated by quantitative Real-time RT-PCR (RT-qPCR). Secondly, effects of circ-BMI1 differential expression on biological function of esophageal cancer cell line Eca109 were analyzed. Effects of circ-BMI1 on cell proliferation, migration and colony forming ability were evaluated by CCK-8, wound healing, and colony-forming assay. Cell apoptosis, drug sensitivity tests were also be conducted. Finally, influence of Eca109 cells differentially expressed by circ-BMI1 on tumorigenicity in nude mice was studied.Results:Expression of circ-BMI1 in serum and tissues of esophageal cancer patients was significantly decreased compared to controls (P < 0.001 and P = 0.003, respectively). Area under the receiver operating characteristic curve (ROC) was 0.726. Cell proliferation, migration and colony forming ability of circBMI1-Eca109 cells were obviously decreased than that of NC-Eca109 cells (P < 0.05). circBMI1-Eca109 cells were more sensitive to 5-fluorouracil and cisplatin, and tumor volume of nude mice in circBMI1-Eca109 group was smaller (P < 0.05).Conclusions:The study indicated that expression of circ-BMI1 was significantly down-regulated in esophageal cancer. Overexpression of circ-BMI1 inhibited proliferation, migration, colony formation of Eca109 cells, and tumor growth of Eca109 cells in nude mice. circ-BMI1 may be a potential target for diagnosis and treatment in esophageal cancer.

Synthesis of Amino Acid Schiff Base Nickel (II) Complexes as Potential Anticancer Drugs In Vitro.

Three hexacoordinated octahedral nickel (II) complexes, [Ni (Trp-sal) (phen) (CH3OH)] (1), [Ni (Trp-o-van) (phen) (CH3OH)]•2CH3OH (2), and [Ni (Trp-naph) (phen) (CH3OH)] (3) (where Trp-sal = Schiff base derived from tryptophan and salicylaldehyde, Trp-o-van = Schiff base derived from tryptophan and o-vanillin, Trp-naph = Schiff base derived from tryptophan and 2-hydroxy-1-naphthaldehyde, phen = 1, 10-phenanthroline), have been synthesized and characterized as potential anticancer agents. Details of structural study of these complexes using single-crystal X-ray crystallography showed that distorted octahedral environment around nickel (II) ion has been satisfied by three nitrogen atoms and three oxygen atoms. All these complexes displayed moderate cytotoxicity toward esophageal cancer cell line Eca-109 with the IC50 values of 23.95 ± 2.54 μM for 1, 18.14 ± 2.39 μM for 2, and 21.89 ± 3.19 μM for 3. Antitumor mechanism studies showed that complex 2 can increase the autophagy, reactive oxygen species (ROS) levels, and decrease the mitochondrial membrane potential remarkably in a dose-dependent manner in the Eca-109 cells. Complex 2 can cause cell cycle arrest in the G2/M phase. Additionally, complex 2 can regulate the Bcl-2 family and autophagy-related proteins.

GPR120 promotes radiation resistance in esophageal cancer via regulating AKT and apoptosis pathway.

The aim of the study is to investigate the role of GPR120 on the biological behavior of esophageal cancer cells in the setting of radiation and explore the mechanism. GPR120 knockdown was fulfilled by siRNA-mediated effects in two esophageal cancer cell lines Eca109 and EC9706. Colony formation, survival fraction calculation, viable cell evaluation by cell counting kit-8 assay and cell apoptosis analysis by phycoerythrin annexin V and 7-amino-actinomycin (7-AAD) staining and the flow cytometry examination was evaluated in Eca109 and EC9706 under the treatment of different radiation dosage. The mechanisms were explored by the evaluation of the Akt pathway and apoptosis protein level. Significantly decreased GPR120 mRNA and protein after GPR120 siRNA treatment compared to control siRNA treatment. Significantly decreased colony formation was found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells at the radiation dosage of 2, 4, 6 and 8 Gy. Moreover, decreased survival fraction number with increased sensitive enhancing ratio was also found in GPR120 siRNA-treated Eca109 and EC9706 cells compared to control siRNA-treated cells. Decreased cell viability and increased cell apoptosis in GPR120 siRNA-treated esophageal cancer cells. GPR120 siRNA decreased the Akt phosphorylation and anti-apoptotic Bcl-2 expression level, but increased pro-apoptotic Bim expression level in esophageal cancer cell lines. GPR120 regulated the biological behavior of the esophageal cancer cells via affecting Akt pathway and apoptosis molecules. Moreover, GPR120 siRNA combined radiation treatment could be a therapeutic choice for esophageal cancer.