Cell Inhibition Rate Research Articles

Synthesis, Crystal Structure, DNA Binding, and Cytotoxicity of a Zn(II) Complex Constructed from Phenylacetic Acid

A novel Zn(II) complex with the formula {[ZnL2(dibe)2]·2H2O}n (synthesized using a carboxylic acid ligand, L = phenylacetic acid, dibe = 4,4′-bipyridine (bipy)) is synthesized at room temperature, characterized and its DNA binding, cleavage, anticancer properties are studied by elemental analysis, infrared spectroscopy, and single crystal X-ray diffraction. The interaction of the complex with fish sperm DNA (FS-DNA) is monitored, which reveals that the complex has the ability to bind to FS-DNA. The complex is further studied for the gel electrophoresis assay with supercoiled plasmid pBR322 DNA. In addition, anticancer activities of the metal complex investigated through MTT in vitro assays, indicate that the complex shows good cytotoxic activity against cancer cell lines. Flow cytometry and apoptosis experiments show that the complex induces apoptosis of HeLa cells, which demonstrates that the complex exhibits a significant cancer cell inhibitory rate.

Combined chemo/photothermal therapy based on mesoporous silica-Au core-shell nanoparticles for hepatocellular carcinoma treatment

Chemotherapy has been widely used for treatment to malignant cancer, such as hepatocellular carcinoma (HCC). Chemotherapeutic effect was not often efficient to achieve totally tumor ablation due to the poor cellular uptake and drug resistance. To address these problems, a novel nanoplatform was constructed based on nontoxic mesoporous silica nanoparticles (MSNs) for a combined chemo/photothermal therapy to enhance tumor cell accumulation and promote toxicity of chemotherapeutic drugs. Prepared MSNs were consisted of Au nanoshell for photothermal conversion and a first-line anti-HCC drug-sorafenib (SO) for chemotherapy. The SO-Au-MSNs could help SO accumulate more in hepatic cancer cells. Under near infrared irradiation, SO-Au-MSNs exerted a high cell inhibition rate which could be attributed to the enhanced toxicity of SO under hyperthermia and synergistic chemo/photothermal therapy. SO-Au-MSNs showed a good compatibility as well as efficient cell cytotoxicity. Overall, SO-Au-MSNs would be a promising candidate for further enhancing the antitumor effect on HCC.

Long non‑coding RNA bladder cancer‑associated transcript 2 contributes to disease progression, chemoresistance and poor survival of patients with colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-associated mortality worldwide. Long non-coding RNAs (lncRNAs) have been revealed to modulate various biological cell processes, and are involved in the initiation and progression of different diseases, including CRC. However, the role of lncRNA bladder cancer-associated transcript 2 (BLACAT2) in CRC has not been defined. The present study aimed to investigate the role of BLACAT2 in CRC. The present study measured the expression levels of BLACAT2 in CRC cells and tissues by reverse-transcription-quantitative polymerase chain reaction, and associations among BLACAT2 expression levels, important clinicopathological parameters and patient survival were statistically evaluated. The functional role of BLACAT2 in metastasis, proliferation and drug resistance was also detected. BLACAT2 was overexpressed in CRC cells and tissues, and high BLACAT2 expression was associated with larger tumor size, and more advanced lymph node (N), metastasis (M) and tumor-NM stages. Additionally, survival analysis demonstrated that patients with high BLACAT2 expression exhibited poor overall survival. Notably, high BLACAT2 expression was identified as an independent risk factor for overall survival. Migration and invasion assays revealed that BLACAT2 promoted migration and invasion, respectively. In addition, overexpression of BLACAT2 increased colony numbers and optical density values of CRC cells in a colony formation assay and an MTT assay, respectively. Furthermore, BLACAT2 levels were significantly increased in 5-fluorouracil-resistant cells, and overexpression of BLACAT2 was markedly associated with a low cell inhibition rate. In conclusion, BLACAT2 overexpression may contribute to the metastasis, proliferation and chemoresistance of CRC cells, and high BLACAT2 expression may be a promising prognostic marker for patients with CRC.

Self-assembled amphiphilic chitosan nanomicelles to enhance the solubility of quercetin for efficient delivery

Quercetin (QCT) has important functions such as antioxidant, anti-inflammatory and anticancer. However, its applications in food and in drug are restricted owing to its poor water solubility. In this work, a novel amphiphilic wall-material chitosan was synthesized via grafting of chitosan with deoxycholic acid (DA) as hydrophobic group and modified N-acetyl-L-cysteine (NAC) as hydrophilic group. Amphiphilic chitosan was self-assembled to load QCT as nanomicelles by a low-cost and inorganic solvent procedure. Both the encapsulation efficiencies (EE) and drug-loading rates (DL) increased when increasing the grafting rate of DA. There was a bursting release of QCT for the QCT-loaded nanomicelles (CS-DA-NAC-QNMs) from 0 to 8 h, and then the release rate decreased gradually. After releasing for 72 h, the final cumulative release percentages were more than 40%. All the QCT-loaded nanomicelles samples showed good hemocompatibility, and their water solubility and biocompatibility increased evidently. What’s more, they exhibited an obvious inhibition rate of A549 cells.

Liraglutide promotes apoptosis of HepG2 cells by activating JNK signaling pathway.

To study the effect and mechanism of liraglutide on the apoptosis of human hepatocellular carcinoma HepG2 cells. HepG2 cell was treated with different concentrations of liraglutide at 0, 1, 10, 100, and 1000 nmol/L. The effect of liraglutide on HepG2 proliferation was detected by Cell Counting Kit-8 (CCK-8) method; the effect of liraglutide on the protein expression of c-Jun NH2-terminal Kinase (JNK) and phosphorylated JNK (p-JNK) was detected by Western blot; the degree of HepG2 apoptosis was observed by flow cytometry, and JNK pathway blocker SP600125 was used to further confirm that liraglutide promoted HepG2 apoptosis by regulating JNK signaling pathway. The proliferation inhibition rate of HepG2 cells increased with time and the increase in the concentration of liraglutide. The proliferation inhibition rate was the strongest when cultured for 48 h, and the IC50 (half maximal inhibitory concentration) was about 100 nmol/L of liraglutide. 100 nmol/L liraglutide was selected as the intervention condition for subsequent use of SP600165. The apoptosis rate of HepG2 cells increased with the increase of liraglutide's concentration. The apoptosis rate of HepG2 cells at blocker SP600125+100 nmol/L liraglutide was significantly lower than that at 100 nmol/L liraglutide alone (p<0.05). There was no significant difference in the expression of JNK protein in HepG2 cells at different concentrations of liraglutide (p>0.05). There was no significant difference in the expression of JNK protein in HepG2 cells using JNK pathway blocker SP600125 (p>0.05), while using JNK pathway blocker SP600125 significantly up-regulated the expression of p-JNK protein in HepG2 cells than 100 nmol/L of liraglutide alone (p<0.05). Liraglutide can promote the apoptosis of hepatocellular carcinoma HepG2 cells in a dose-dependent manner, and its mechanism may act by promoting the activation of the JNK signaling pathway.

New Polylactic Acid Multifunctional Ultrasound Contrast Agent Based on Graphene Oxide as the Carrier of Targeted Factor and Drug Delivery.

In recent years, the development of ultrasound contrast agents has encouraged their use as a drug system for diagnosis and therapy. In this paper, polylactic acid (PLA) composite microbubbles (FA/DOX/GO/DOX/PLA) were prepared with graphene oxide (GO) as a carrier of the targeted factor folic acid (FA) and doxorubicin (DOX) by the multiple emulsification–solvent evaporating process. Appearance, particle size, and zeta potential of PLA composite microbubbles were characterized by using a nanoparticle size analyzer and transmission electron microscopy. Breast cancer cells MCF-7 were used to evaluate the antitumor activity of PLA composite microbubbles in vitro by using the CCK-8 and acridine orange staining method. The ultrasonic imaging effect of PLA composite microbubbles was investigated in New Zealand white rabbits by the Doppler color ultrasound imaging system. With Kunming mice as the research model, the acute toxicity of PLA composite microbubbles was examined. The experimental results showed that the prepared PLA composite microbubbles presented a hollow and spherical shape with a particle size of 600 nm or so and a zeta potential of −37.5 ± 10.0 mV. They had a good effect of the enhancing imaging, and clear ultrasound imaging can be obtained. PLA composite microbubbles showed a significant proliferation inhibition effect on breast cancer cells MCF-7 in a dose-dependent manner. After PLA composite microbubbles were modified by FA, they were good for targeting FA receptors on the surface of MCF-7 cells, which increased the inhibition rate of the tumor cells. LD50 of PLA composite microbubbles was 87.529 mg·kg–1; the mice did not show the acute toxicity when the dose of composite microbubbles was lower than this value.

C18H17NO6 and Its Combination with Scutellarin Suppress the Proliferation and Induce the Apoptosis of Human Glioma Cells via Upregulation of Fas-Associated Factor 1 Expression.

Background Glioma is the most common malignant brain tumor and the patients are prone to poor prognosis. Due to limited treatments, new drug exploration has become a general trend. Therefore, the objective of this study is to investigate the effect of the new drugs C18H17NO6 and its combination with Scutellarin on glioma cells and the underlying mechanism. Method U251 and LN229 cells were administrated with C18H17NO6 and its combination with Scutellarin. The proliferation ability of glioma cells was determined by cell counting kit-8, plate clone formation assay, and EdU incorporation assay. The cell cycle and apoptosis detection were detected by flow cytometry. Moreover, TUNEL assay was also used for cell apoptosis analysis. Then, the transfer ability of cells was achieved through wound healing assay. Furthermore, polymerase chain reaction (PCR) test and western bolt analysis were used to detect the mRNA expression and protein expression, respectively. Lastly, immunofluorescence was for the purity identification of astrocyte. Result The results showed that, with the increasing dose of C18H17NO6, the cell inhibition rate, the cells in G1 phase, and the apoptosis rate were gradually increased, but the clone number, proliferation rate, and the cells in G2 and S phases were gradually decreased in comparison with control group. However, with the increase of C18H17NO6, the transferred rate of U251 and LN229 was not significantly augmented, expect that on U251 in C18H17NO6 5 μM group. In addition, Scutellarin 200 μM has little effect on proliferation, with the inhibition rate 10-20% and proliferation rate except U251 in Scutellarin 200 μM group similar to that in control group. Moreover, compared to control group, Scutellarin 300 μM increased the U251 cells in G2 and S phases and the apoptosis rate of LN229 but decreased the LN229 cells in G2 and S phases. Besides, in Scutellarin 200 μM group, the transfer ability of LN229 was inhibited, but not in U251. Furthermore, if C18H17NO6 was combined with Scutellarin 200/300μM, the proliferation and transferred ability were suppressed and the apoptosis was elevated in LN229 cell in comparison with C18H17NO6 alone. Dramatically, the combined effect on U251 was the exact opposite. Importantly, there was little toxicity on astrocyte under the dose of C18H17NO6 and Scutellarin in the study. In molecular level, the mRNA and protein expression of Fas-associated factor 1 (FAF1) expression in U251 and LN229 were upregulated by C18H17NO6 and its combination with Scutellarin, especially the protein expression. Conclusion C18H17NO6 could efficiently suppress cell proliferation and induce cell apoptosis in glioma cells, and its combination with Scutellarin had a promoting effect, in which the underlying mechanism referred to the upregulation of Fas-associated factor 1.

Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Three novel complexes, [Zn (tib)2·(H2O)2]·(NO3)2 (1), [Co (tib)2]·2NO3 (2) and [Co2(tib)2(btc)]·H2O (3) [H4btc = 1,2,4,5‐benzenetetracarboxylic acid; H2tib = 1,3,5‐tris(1‐imidazolyl)benzene], were synthesized and characterized by single‐crystal X‐ray, IR and elemental analysis. The interaction of these complexes with FS‐DNA (fish sperm DNA) was monitored, and binding constants were determined using UV/Vis, which revealed that they have the ability to bind to FS‐DNA. DNA‐binding constants (K) for the three complexes were 2.2 × 104 m−1, 0.7 × 104 m−1 and 0.09 × 104 m−1, respectively. The interaction capacity of the complexes with FS‐DNA has been investigated by fluorescence spectroscopy. Stern–Volmer quenching plot values for complexes 1, 2 and 3 were 0.3784, 0.1028 and 0.076, respectively. The viscosity measurement suggested that complexes 1, 2 and 3 interact with DNA in an intercalation mode. In addition, anti‐cancer activities of these complexes investigated through MTT assays in vitro indicated that the complexes showed good cytotoxic activity against cancer cell lines. Cytotoxic activity of test complexes against two different cancer cell lines (HeLa and KB cells) showed significant cancer cell inhibition rates. Flow cytometry experiments and morphological apoptosis studies showed that the complexes induced apoptosis of HeLa tumor cell lines. Finally, a further molecular docking technique was employed to confirm the binding of the complexes toward the molecular target DNA.

Icotinib inhibits proliferation and epithelial-mesenchymal transition of non-small cell lung cancer A549 cells.

Objective: To investigate the inhibitory effect of Icotinib on proliferation and epithelial-mesenchymal transition of A549 cells. Methods: A549 cells were treated with Icotinib of different concentrations. The morphology of the cells was observed by inverted phase contrast microscope. The effect of different concentrations of Icotinib on the proliferation inhibition rate of A549 cells was detected by MTT assay. Flow cytometry was used to detect effect of Icotinib on the apoptosis rate of A549 cells. ELISA assay was used to detect the expression of EMT-related proteins, E-cadherin, N-cadherin, Vimentin and fibronectin, in A549 cells cultured supernatant. Transwell assay was used to examine the effects of different concentrations of Icotinib on the migration and invasion abilities of A549 cells. Results: Morphological changes were observed after A549 cells exposed to different concentrations of Icotinib for 48 hours. The inhibition rate of proliferation for each treatment group increased from MTT assay results. Flow cytometry results showed that cell apoptosis rate was significantly increased. Expression of E-cadherin was up-regulated and expression of N-cadherin, Vimentin and fibronectin were down-regulated from ELISA results. A549 cell migration and invasion abilities were significantly suppressed by Icotinib at different concentrations. Conclusion: Icotinib inhibits A549 cell proliferation, migration and invasion in both concentration and time-dependent manners, in turn it promotes A549 cell apoptosis in the same way. Icotinib also inhibits epithelial-mesenchymal transition by regulating EMT-related proteins expression in A549 cells.

Synthesis, crystal structure, DNA binding, and cytotoxicity of a Zn(II) complex constructed from phenylacetic acid

A novel Zn(II) complex with the formula {[ZnL2(dibe)2]⋅2H2O}n (synthesized using a carbo­xylic acid ligand, L = phenylacetic acid, dibe = 4,4'-bipyridine (bipy)) is synthesized at room temperature, characterized and its DNA binding, cleavage, anticancer properties are studied by elemental analysis, infrared spectroscopy, and single crystal X-ray diffraction. The interaction of the complex with fish sperm DNA (FS-DNA) is monitored, which reveals that the complex has the ability to bind to FS-DNA. The complex is further studied for the gel electrophoresis assay with supercoiled plasmid pBR322 DNA. In addition, anticancer activities of the metal complex investigated through MTT in vitro assays, indicate that the complex shows good cytotoxic activity against cancer cell lines. Flow cytometry and apoptosis experiments show that the complex induces apoptosis of HeLa cells, which demonstrates that the complex exhibits a significant cancer cell inhibitory rate.

Effect of STAT3 decoy oligodeoxynucleotides mediated by ultrasound-targeted microbubbles combined with ultrasound on the growth of squamous cell carcinoma of the esophagus.

Effect of STAT3 decoy oligodeoxynucleotides (ODN) transduced by ultrasound microbubbles combined with ultrasound on the growth of esophageal squamous cell carcinoma and its mechanism were analyzed. EC9706 cells were cultured in vitro and divided into four groups: group E (ultrasound microbubble + ultrasound irradiation), group P (liposome + ultrasound irradiation), group C (ultrasound), and group CC (ultrasound microbubbles). Mutant ODNs were used in groups E and P and the control group was group EC and PC, respectively. Immunofluorescence assay and flow cytometry were used to detect the transfection efficiency of each group. MTT colorimetric assay was performed to analyze the inhibition rate in each group. The effect of STAT3 decoy ODN on the proliferation of esophageal squamous carcinoma cells was calculated. Revese transcription-quantitative PCR (RT-qPCR) and western blotting were performed to detect the expression of the STAT signaling pathway downstream of gene expression levels. The model of subcutaneous transplantation of nude mice was used to show the effect of different transfections and STAT3 decoy ODN on the weight and volume of the transplanted tumor in mice. The cell inhibition rate was higher in group E than in groups P (F=8.382, P<0.001) and CC (F=6.469, P<0.001). Compared with groups EC, PC and C, respectively, the mRNA expression of STAT3, bcl-xL and Cyclin D1 decreased in groups E, P and CC (F=5.328, P<0.001). The weight and volume of nude mice in groups E, P and CC exhibited an inhibitory effect on the weight and volume of nude mice. Ultrasound irradiation combined with ultrasound microbubbles is an effective transfection method. The transfection of STAT3 decoy ODN can significantly inhibit the activity of esophageal squamous cell carcinoma cells and enhance apoptosis of cells, which has potential clinical value.

Methotrexate-induced apoptosis in human ovarian adenocarcinoma SKOV-3 cells via ROS-mediated bax/bcl-2-cyt-c release cascading.

IntroductionThe communication between a substance and a cell may depend on whether the cell is normal or pathological. The disease cells and drug interaction may occasionally overcome beneficial action of the drug; subsequently, it is important to investigate the effect of the drug in both the normal and target cells. This study aimed to evaluate the methotrexate (MTX) antiproliferative effect and explore the mechanistic approach to investigate the cell death index in SKOV-3 ovarian cells during treatment with MTX.MethodsIn vitro studies of SKOV-3 cells were examined by tetrazolium assay after exposure to various concentrations of MTX. Moreover, reactive oxygen species (ROS) generation, mitochondrial membrane potential, DNA damage, and AO/EtBr staining morphological analysis of necrotic/apoptotic cells were detected; cellular impairment in mitochondria and DNA was confirmed by JC-1 mitotracker/DAPI, respectively, and cell death pathway markers; bax/bcl-2 were analyzed.ResultsA dose-dependent antiproliferative effect of MTX treatment was observed in SKOV-3 cells; the prominent inhibitory concentration was 40 µM of MTX (P<0.01). The growth inhibition rates of the cancer cells reached 24.07% in MTX. The MTX showed increase in ROS generation and mitochondrial depolarization, and DNA integrity cells collectively advocated the apoptotic cell death at higher concentration. In addition, the results of reverse transcription polymerase chain reaction also supported the apoptosis by upregulating the bax and downregulating the bcl-2 (P<0.01). Thus the MTX moderately provokes apoptosis.ConclusionOur findings suggest that MTX acts on SKOV-3 cancer cells by increasing intracellular ROS levels, leading to DNA damage and altering the MMP along with apoptotic gene upregulation. This mechanism may provide new therapeutic targets to improve tumor treatment.

Long noncoding RNA SNHG15 serves as an oncogene and predicts poor prognosis in epithelial ovarian cancer.

ObjectiveThis study aims to investigate the functional role of long noncoding RNA SNHG15 in epithelial ovarian cancer (EOC).Materials and methodsThe expression of SNHG15 was measured in EOC cells and tissues using qRT-PCR. The correlation of SNHG15 expression and the clinicopathological characters was statistically analyzed. The prognosis of patients with different clinical features in the high/low SNHG15 expression groups were calculated. Moreover, univariate and multivariate Cox regression analyses were performed to identify the risk factors for poor overall survival (OS) and progression-free survival (PFS). The effect of SNHG15 on the migration and invasion was evaluated using Transwell and Matrigel, respectively. The proliferation ability of EOC cells was tested using colony formation and MTT assay. The influence of SNHG15 on the cisplatin resistance was detected by measuring cell inhibition rate and cell viability.ResultsSNHG15 was upegulated in EOC cells and tissues. High SNHG15 expression was correlated with EOC progression and predicted poor OS and PFS in different subgroups of EOC patients. Moreover, multivariate Cox regression analysis defined high SNHG15 expression as an independent risk factor for poor OS and PFS. Furthermore, functional assays showed that the overexpression of SNHG15 promoted migration and invasion, while the loss of SNHG15 suppressed migration and invasion. Furthermore, the proliferation of EOC cells was improved after the ectopic expression of SNHG15, which was suppressed with SNHG15 deficiency. In addition, cisplatin-resistant EOC cells were established for detecting the effect of SNHG15 on EOC chemoresistance. The results showed that cisplatin-resistant EOC cells exhibited much higher levels of SNHG15 expression than controls, and SNHG15 contributed to the chemoresistance of EOC cells.ConclusionThis study confirms that SNHG15 contributes to the migration, invasion, proliferation, and chemoresistance of EOC. SNHG15 may serve as a potential therapeutic target and prognostic biomarker of EOC patients.

Two MnII, CuII complexes derived from 3,5‐bis(1‐imidazoly) pyridine: Synthesis, DNA binding, Molecular docking and cytotoxicity studies

Two complexes [MnL2 (H2O)2]·2ClO4 (complex 1) and [CuL(H2O)3]·2NO3 (complex 2) (where L = 3,5‐bis(1‐imidazoly) pyridine) were designed and synthesized. The structures of the complexes were characterized by X‐ray crystallography, elemental analyses, and infrared spectrum. The interaction capacity of the complexes with calf thymus DNA has been investigated by UV and fluorescence spectroscopy. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. Efficient binding properties of DNA were established by UV–vis, fluorescence, and gel electrophoresis. The intrinsic binding constants (Kb) were calculated to be 0.1524, 0.1041 for complexes 1–2, respectively. The cytotoxic activity of the two complexes exhibited a higher cytotoxicity against HeLa cell lines and lower cytotoxicity toward the normal cell lines. Flow cytometry demonstrated the cancer cell inhibitory rate of two complexes. Furthermore, computer‐aided molecular docking studies were performed to visualize the binding mode of the drug candidate at the molecular level. Interestingly, complex 1 exhibited a significant cancer cell inhibitory rate than cisplatin and other complexes.

Lanthanum-Containing Magnesium Alloy with Antitumor Function Based on Increased Reactive Oxygen Species

Developing antitumor implants is of great significance to repair tumor-induced bone defects and simultaneously prevent bone tumor recurrence. The tumor cells, compared to normal cells, have a high reactive oxygen species level. They are vulnerable to oxidative insults under increased intrinsic oxidative stress. The lanthanum (La) ion with high phospholipid binding ability can open the mitochondrial permeability transition pore, which blocks the electron transport chain in the mitochondria, and consequently increases reactive oxygen species level. In this study, La was alloyed to Mg-6Zn-0.5Zr (ZK60) through selective laser melting technology. The results indicated that the mitochondrial membrane potential dropped whilst the reactive oxygen species increased as the La content increased. ZK60-1.0La revealed a high cell inhibition rate of 61.9% for bone tumor cell and high cell viability of 91.9% for normal cells, indicating that the alloy could induce bone tumor cell death, as well as exhibit good biocompatibility for normal cell. In addition, its degradation rate 1.23 mm/year was lower than that of ZK60 alloy 2.13 mm/year, which was mainly attributed to the grain refinement.

Effects of propofol on human cholangiocarcinoma and the associated mechanisms.

Cholangiocarcinoma (CCA) is the most common type of biliary duct malignancy. Propofol is a fast-acting intravenous anesthetic, which also exerts an anti-cancer effect. The aim of the current study was to explore the effects of propofol on human CCA and the associated mechanisms in vitro. The results indicated that as concentration (0, 1, 5 and 10 µg/ml) of propofol and treatment time (24, 48 and 72 h) increased, the cell inhibition rate of human CCA QBC939 cells increased. Furthermore, treatment with various concentrations of propofol for 48 h resulted in a decrease in migration and invasion capacity in QBC939 cells. Propofol also induced the apoptosis of QBC939 cells and cell cycle arrest in G1 phase. Propofol treatment increased the expression level of Bax and decreased that of Bcl-2. In addition, the effects of propofol on gene expression were evaluated, including Wnt3α, β-catenin, Snail1 and c-myc in the Wnt/β-catenin signaling pathway. It was identified that as the concentration of propofol increased, the expression of these genes decreased. In conclusion, the current results indicate that propofol is a promising therapeutic agent for the treatment of CCA.

Puerarin in inducing apoptosis of bladder cancer cells through inhibiting SIRT1/p53 pathway.

Regulatory effect of puerarin on bladder cancer T24-cell apoptosis and its possible mechanism were investigated. The experimental subjects were divided into the experimental group, the control group and the blank control group, and the cell inhibition rates after treatment were detected, respectively. Then, subjects were further divided into the control group, the puerarin group (treated with puerarin), the agonist group [treated with silent information regulator 1 (SIRT1) agonist SRT1720], the inhibitor group (treated with SIRT1 inhibitor EX527) and the combination group (treated with SRT1720, and then with puerarin). Apoptosis in each group was detected via flow cytometry, and the expression of apoptosis-related proteins, and SIRT1 and p53 proteins in each group was detected via western blotting. Moreover, the expression of SIRT1 and p53 messenger ribonucleic acid (mRNA) was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The inhibition rate of bladder cancer T24 cells was significantly increased after treatment with puerarin at different concentrations. Compared with those in the normal control group, the inhibition rates at 24, 48 and 72 h after treatment with puerarin were significantly increased (p<0.05). Compared with those in the control group, the apoptosis rate of T24 cells was remarkably increased after treatment with different doses of puerarin or EX527, and the expression level of apoptosis-related protein Bcl-2-associated X protein (Bax) was also significantly increased, but the expression level of B-cell lymphoma 2 (Bcl-2) was decreased, and both the protein and mRNA expression levels of SIRT1 and p53 also significantly declined. Compared with those in the puerarin group, the apoptosis rate in the combination group was decreased, and the expression level of apoptosis-related protein Bax was also significantly decreased, but the expression level of Bcl-2 was increased, and SIRT1 and p53 protein expression levels were also remarkably increased. Puerarin can inhibit the proliferation of bladder cancer T24 cells and induce apoptosis, and the possible mechanism is related to the inhibition of SIRT1/p53 signaling pathway.

Inhibition of PLA2G4A Reduces the Expression of Lung Cancer-Related Cytokines.

Phospholipase A2-IVA (PLA2G4A) is the most abundant subtype of cytoplasmic phospholipase A2 (cPLA2) and is an important enzyme in tumor development. Our study aimed to explore the role of PLA2G4A in the regulation of lung cancer. The contents of cell-related cytokines (microsomal prostaglandin E synthase-1 [mPGES], PGE2, and prostacyclin [PGI2]) in A549 cells were analyzed by ELISA kits. Cell counting kit-8 (CCK8) was used to detect the effects of inhibitor of cPLA2 (arachidonyl trifluoromethyl ketone [AACOCF3]) on the proliferation of A549 cells. The migration and invasion of A549 cells were tested by cell scratch wound healing assay and transwell assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the effect of inhibitor AACOCF3 on the expression of related mRNA and protein in A549 cells. ELISA result showed that the levels of mPGES, PGE2, and PGI2 in control group were significantly higher than those in the AACOCF3 group. Cell inhibition rate in the control group was significantly lower than that in the AACOCF3 group. The percentage of wound healing in the control group was significantly higher than that in the AACOCF3 group. Meanwhile, the relative invasive number of cells in the control group was significantly higher than those in the AACOCF3 group. The expression levels of related mRNA of PLA2G4A and cyclooxygenase-2 (COX-2) and the expression levels of mPGES, COX-1, and COX-2 protein in the control group were significantly higher than those in the AACOCF3 group. Our research showed that PLA2G4A was involved in migration and invasion of lung cancer cells.

Enhanced response of tamoxifen toward the cancer cells using a combination of chemotherapy and photothermal ablation induced by lentinan-functionalized multi-walled carbon nanotubes

A lentinan (LEN) functionalized multi-walled carbon nanotubes (MWCNTs) drug delivery system, using tamoxifen (TAM) as a model anticancer agent, was developed by a simple non-covalent approach. This developed system (MWCNTs-TAM-LEN) possessed good stability, water dispersibility and extraordinary photothermal properties. It was demonstrated by the in vitro experiments that MWCNTs-TAM-LEN had enhanced cellular uptake, antitumor activity and cell apoptosis on Mcf-7 cells in comparison with TAM and MWCNTs-TAM. The cell inhibition rate and apoptosis rate of Mcf-7 cells treated by MWCNTs-TAM-LEN with near-infrared (NIR) were 67.1% and 66.5% higher than that of equivalent concentration of TAM with NIR irradiation treatment, respectively. The enhanced antitumor efficacy of MWCNTs-TAM-LEN was realized via the synergistic function of chemotherapy and photothermal ablation under NIR laser irradiation.

Mifepristone inhibits proliferation, migration and invasion of HUUA cells and promotes its apoptosis by regulation of FAK and PI3K/AKT signaling pathway.

PurposeThe aim was to investigate mifepristone effects on endometrial carcinoma and the related mechanism.MethodsHHUA cells were treated with DMEM containing different concentrations of mifepristone. HHUA cells treated with 100 μmol/L mifepristone were named the Mifepristone group. HHUA cells co-transfected with pcDNA3.1-PI3K and pcDNA3.1-AKT overexpression vectors were treated with 100 μmol/L mifepristone and named the Mifepristone + PI3K/AKT group. mRNA expression was detected by quantitative reverse transcription PCR. Protein expression was performed by Western blot. Cell proliferation was conducted by MTT assay. Wound-healing assay was conducted. Transwell was used to detect cells migration and invasion. Apoptosis detection was performed by flow cytometry.ResultsMifepristone inhibited HHUA cells proliferation in a dose-dependent manner. Compared with HHUA cells treated with 0 μmol/L mifepristone, HHUA cells treated by 50–100 μmol/L mifepristone had a lower wound-healing rate, a greater number of migrating and invasive cells (P<0.01), as well as a higher percentage of apoptotic cells and Caspase-3 expression (P<0.01). When HHUA cells were treated with 50–100 μmol/L of mifepristone, FAK, p-FAK, p-PI3K and p-AKT relative expression was all significantly lower than HHUA cells treated with 0 μmol/L of mifepristone (P<0.01). Compared with the Mifepristone group, HHUA cells of the Mifepristone + PI3K/AKT group had a lower cell growth inhibition rate and percentage of apoptotic cells (P<0.01).ConclusionMifepristone inhibited HUUA cells proliferation, migration and invasion and promoted its apoptosis by regulation of FAK and PI3K/AKT signaling pathway.