Cell Lines MKN-45 Research Articles

5-aminolevulinic acid and sodium ferrous citrate decreased cell viability of gastric cancer cells by enhanced ROS generation through improving COX activity

BackgroundMitochondrial dysfunctions are related to cancer development.. 5-aminolevulinic acid (ALA) is used for photodynamic therapy (PDT). In this PDT, protoporphyrin IX (PpIX), which is converted from ALA, can generate reactive oxygen species (ROS) that kill the cancer cell. ALA is also reported to promote cytochrome c oxidase (COX) activity, which can generate ROS itself. Therefore, this study focused on the effect of ALA during PDT. In addition, in the previous study, sodium ferrous citrate (SFC) is reported to increase COX activity. So, this study also aims to improve the COX activity by the addition of SFC that can promote ROS generation, which has a cytotoxic effect. MethodsIn this study, we used ALA and SFC, then evaluated the effects of the treatment on the human gastric cancer cell line MKN45, including the induction of cell death. ResultsThis study showed that treatment with ALA and SFC increases intracellular heme and heme proteins. Moreover, COX activity was promoted, resulting in the production of intracellular reactive oxygen species (ROS), which eventually reduced the cell viability in human gastric cancer cell line MKN45. ConclusionOur study can detect ROS generation with ALA and SFC. Furthermore, we found this generation of ROS has a cytotoxic effect. Therefore, this phenomenon contributes to the effect of PDT.

WITHDRAWN: In vitro anti-human gastric cancer property of silver nanoparticles green-synthesized by Vitis vinifera leaf aqueous extract

We report the green synthesis of nontoxic, stable, and small-size silver nanoparticle by Vitis vinifera leaf aqueous extract with reducing/capping ability without any toxic reducing agents. The in situ prepared Ag NPs were characterized by Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM) and Ultraviolet–visible spectroscopy (UV-Vis) study. The treated cells with Ag NPs were assessed by MTT assay for 48h about the cytotoxicity and anti-human gastric cancer properties on gastric cancer cell lines i.e. NCI-N87, MKN45 and GC1415. The IC50 of Ag NPs were 72, 51 and 43 µg/mL against NCI-N87, MKN45 and GC1415 cell lines, respectively. The viability of malignant gastric cell lines reduced dose-dependently in the presence of Ag NPs. In the antioxidant test, the IC50 of Ag NPs and BHT against DPPH free radicals were 81 and 45 µg/mL, respectively.

Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer.

Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10B-labeled BPA (10B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague–Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue.

Modulation of cisplatin resistance in gastric cancer by LncRNA SNHG15

Background: The role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) in cisplatin-resistance was studied in gastric cancer.
 Methods: The relative SNHG15 expression and its correlation with survival were assayed on the Cancer Genome Atlas data and confirmed with the clinical samples we collected. Cisplatin-resistant MKN45 cell line (MKN45 CR) was established. SNHG15 plasmid and SNHG15 shRNA plasmid were transfected into MKN45 cells and MKN45 CR cells. Colony formation analysis and cell counting kit-8 assay were utilized to determine cell proliferation and viability. The binding between SNHG15 and zeste 2 polycomb repressive complex 2 subunit (EZH2) was testified with RNA immunoprecipitation (RIP). The promoter activity of phosphatase and tensin homolog (PTEN) was evaluated by luciferase reporter assay.
 Results: High SNHG15 expression was correlated with the poor overall survival of gastric cancer patients, and cisplatin treatment can induce time and dose-dependent up-regulation of SNHG15. At the same time, SNHG15 overexpression could promote the cisplatin resistance, while SNHG15 inhibition could diminish the cisplatin resistance. RIP assays confirmed the interaction of SNHG15 with EZH2. More importantly, SNHG15 inhibited PTEN promoter activity by reducing EZH2 recruitment in MKN45 CR cells.
 Conclusion: SNHG15 epigenetically prohibits PTEN expression by recruiting EZH2 in gastric cancer cisplatin-resistant cells.

Synthesis of a 2-nitroimidazole derivative N-(4-[18F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)-acetamide ([18 F]FBNA) as PET radiotracer for imaging tumor hypoxia

BackgroundTissue hypoxia is a pathological condition characterized by reducing oxygen supply. Hypoxia is a hallmark of tumor environment and is commonly observed in many solid tumors. Non-invasive imaging techniques like positron emission tomography (PET) are at the forefront of detecting and monitoring tissue hypoxia changes in vivo.ResultsWe have developed a novel 18F-labeled radiotracer for hypoxia PET imaging based on cytotoxic agent benznidazole. Radiotracer N-(4-[18F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)acetamide ([18F]FBNA) was synthesized through acylation chemistry with readily available 4-[18F]fluorobenzyl amine. Radiotracer [18F]FBNA was obtained in good radiochemical yields (47.4 ± 5.3%) and high radiochemical purity (> 95%). The total synthesis time was 100 min, including HPLC purification and the molar activity was greater than 40 GBq/µmol. Radiotracer [18F]FBNA was stable in saline and mouse serum for 6 h. [18F]FBNA partition coefficient (logP = 1.05) was found to be more lipophilic than [18F]EF-5 (logP = 0.75), [18F]FMISO (logP = 0.4) and [18F]FAZA (logP = − 0.4). In vitro studies showed that [18F]FBNA accumulates in gastric cancer cell lines AGS and MKN45 under hypoxic conditions.ConclusionsHence, [18F]FBNA represents a novel and easy-to-prepare PET radioligand for imaging hypoxia.

STUDY ON THE ISOLATION AND BIOACTIVITY ASSAY OF SOME COMPOUNDS FROM Nelumbo nucifera GAERTN SEEDS COLLECTED AT TINH TAM LAKE, THUA THIEN HUE, VIETNAM

In this study, we isolated and purified compounds from the n-Butanol segment of seed Concave white Lotus variety (N. nucifera) collected at Tinh Tam Lake, Thua Thien Hue province based on classical column chromatographic methods. Research results have obtained three compounds namely: Nuciferin (NH2 : C19H21NO2), Armepavine (NH8 : C19H23O3N), and Anonaine (NH11 : C17H15NO2). At the concentration of 100 µg/mL, Nuciferin was the highest DPPH free radical scavenging activity substance reaching of 94.620 ± 0.657%, followed by Armepavine (74.019 ± 2.400%) and Anonaine (61.151 ± 2.349 %). The IC50 values obtained from these substances were 30.031 ± 1.506 µg/mL (Nuciferin), 43.093 ± 14.215 µg/mL (Armepavine) and 68.217 ± 6.214 µg/mL (Anonaine) respectively. The cytotoxicity results of three active ingredients showed the very low activity of the investigated substances at the studied concentrations. The IC50 value cannot be determined in the concentration range from 0.8; 4; 20 and 100 µg/mL. At a concentration of 100 µg/mL, Nuciferin gave the best inhibitory activity against the human gastric cancer cell line MKN7 (23.800%), Armepavine showed the highest inhibitory activity against the oral carcinoma cell line KB (12.320%) and Anonaine showed the best inhibitory activity against the human skin cancer cell line SK-Mel-2 (19.720%). Our results initially show the prospect of using Concave white Lotus seeds as functional foods to support and improve human health.

Fabrication of γ-Fe2O3@C/PIDA nanosphere to stabilize silver nanoparticles: Engineered nanostructure to bioactivity and antimicrobial activity

Bacteria contamination in drinking water and medical products poses serious threats to the environment and public health. Therefore, the design and synthesis of green-based nanostructures to eliminate bacteria contaminants from the aquatic environment have remained a huge challenge for biomedical and environmental purposes. Herein, the fabricated silver nanoparticles (Ag NPs) supported on propyliminodiacetic acid (PIDA)-functionalized γ-Fe2O3@carbon nanospheres were successfully engineered. The morphology and structure features of the core–shell nanocomposites were investigated with FESEM, TEM, and AFM. From the VSM analysis, the saturation magnetization of the nanocomposite obtained 20.18 emu/g, which provided facile separation of the catalyst from reaction mixtures using an external magnet. The proposed core–shell nanocomposite in this study showed remarkable antibacterial activity in Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The MBC amount for both strains was obtained at 512 μg/mL. Furthermore, MIC for S. aureus and E. coli was achieved at 128 and 256 μg/ml, respectively. Meanwhile, the decrease in cell viability was indicated at 21% for the MKN45 cell line after 72 h treatment. This novel nanostructure with excellent antimicrobial activity holds promise in combating public health concerns and provides a new horizon for biomedical and environmental applications.

Functions and Clinical Significance of CACNA2D1 in Gastric Cancer.

Voltage-gated calcium channels form as a complex of several subunits, among which the function of CACNA2D1, one of the genes encoding the α2δ subunit, remains unclear. The aim of our study was to investigate the role of CACNA2D1 and evaluate the efficacy of amlodipine, a blocker of CACNA2D1, in the treatment of gastric cancer (GC). Knockdown experiments were performed on the human GC cell lines MKN7 and HGC27 using CACNA2D1 small interfering RNA (siRNA), and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical (IHC) analysis was conducted on samples obtained from 196 GC patients who underwent curative gastrectomy. In addition, the antitumor effects of amlodipine were investigated using a xenograft model. Cell proliferation, migration, and invasion were suppressed in CACNA2D1-depleted cells, and apoptosis was induced. The results of the microarray analysis showed that the apoptosis signaling pathway was enhanced via p53, BAX, and caspase 3 in CACNA2D1-depleted cells. A multivariate analysis identified high CACNA2D1 expression levels, confirmed by IHC, as an independent poor prognostic factor in GC patients. Moreover, subcutaneous tumor volumes were significantly smaller in a xenograft nude mouse model treated with a combination of amlodipine and cisplatin than in a model treated with cisplatin alone. The present study indicates that CACNA2D1 regulates the apoptosis signaling pathway and may have potential as a biomarker for cancer growth and as a therapeutic target for GC.

Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8

The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe2+. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe2+ retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer.

Autonomous and intercellular chemokine signaling elicited from mesenchymal stem cells regulates migration of undifferentiated gastric cancer cells.

Accumulating evidence demonstrates that bone marrow (BM)-derived mesenchymal stem cells (MSCs) play critical roles in regulating progression of various types of cancer. We have previously shown that Wnt5a-Ror2 signaling in MSCs induces expression of CXCL16, and that CXCL16 secreted from MSCs then binds to its cognate receptor CXCR6 on the surface of an undifferentiated gastric cancer cell line MKN45 cells, eventually leading to proliferation and migration of MKN45 cells. However, it remains unclear about a possible involvement of another (other) cytokine(s) in regulating progression of gastric cancer. Here, we show that CXCL16-CXCR6 signaling is also activated in MSCs through cell-autonomous machinery, leading to upregulated expression of CCL5. We further show that CCR1 and CCR3, receptors of CCL5, are expressed on the surface of MKN45 cells, and that CCL5 secreted from MSCs promotes migration of MKN45 cells presumably via its binding to CCR1/CCR3. These data indicate that cell-autonomous CXCL16-CXCR6 signaling activated in MSCs upregulates expression of CCL5, and that subsequent activation of CCL5-CCR1/3 signaling in MKN45 cells through intercellular machinery can promote migration of MKN45 cells. Collectively, these findings postulate the presence of orchestrated chemokine signaling emanated from MSCs to regulate progression of undifferentiated gastric cancer cells.

A-Kinase Interacting Protein 1 Promotes Cell Invasion and Stemness via Activating HIF-1α and β-Catenin Signaling Pathways in Gastric Cancer Under Hypoxia Condition.

BackgroundA-Kinase interacting protein 1 (AKIP1) relates to gastric cancer growth, metastasis, and prognosis, while its regulation on gastric cancer invasion and stemness under hypoxia microenvironment is not reported. Therefore, this study aimed to explore this topic to uncover AKIP1’s role in gastric cancer under hypoxia.MethodsGastric cancer cell lines AGS and MKN45 were cultured under hypoxia condition, then transfected with AKIP1 or negative control (NC) overexpression plasmid or AKIP1 or NC knockdown plasmid. Furthermore, rescue experiments were conducted by transfecting HIF-1α or β-catenin overexpression plasmid, combined with AKIP1 or NC knockdown plasmid. Afterward, cell invasion, CD133+ cell proportion, sphere number/1,000 cells, and HIF-1α and β-catenin pathways were measured.ResultsThe invasive cell count, CD133+ cell proportion, and sphere number/1,000 cells were enhanced in both AGS cells and MKN45 cells under hypoxia, and AKIP1 expression was also elevated. AKIP1 knockdown inhibited cell invasion, CD133+ cell proportion, sphere number/1,000 cells, HIF-1α, vascular endothelial growth factor (VEGF), β-catenin, and calcium-binding protein (CBP) expressions in AGS cells and MKN45 cells under hypoxia, while AKIP1 overexpression presented with the opposite effect. Then, in rescue experiments, HIF-1α overexpression and β-catenin overexpression both promoted cell invasion, CD133+ cell proportion, and sphere number/1,000 cells, which also attenuated the effect of AKIP1 knockdown on these functions in AGS cells and MKN45 cells.ConclusionAKIP1 promotes cell invasion and stemness via activating HIF-1α and β-catenin signaling pathways in gastric cancer under hypoxia condition.

Identification of the upstream regulators of KDM5B in gastric cancer

AimsLysine-specific demethylase 5B (KDM5B) is an epigenetic regulator of chromatin that catalyzes the demethylation of histone 3 lysine 4. It is overexpressed in multiple cancer types and acts as a therapeutic target in cancer therapy. Nevertheless, its upstream regulatory pathway is not completely understood, prompting the search for the underlying biological factors driving KDM5B overexpression. Materials and methodsA comprehensive analysis was performed to examine the association between KDM5B overexpression and copy number variation (CNV), somatic mutation, mRNA expression, miRNA expression, and clinical characters from The Cancer Genome Atlas database. Coexpression and function enrichment analyses were performed with KDM5B-coexpressed genes. The gastric cancer (GC) cell line MKN45 was utilized to verify the regulation of KDM5B using the transcription factor (TF) Yin Yang 1 (YY1) and miR-29a-3p. Key findingsKDM5B was overexpressed and associated with poor prognosis in GC. KDM5B upregulation was driven by CNV amplification and DNA hypomethylation rather than by KDM5B mutations. Enrichment analysis revealed that KDM5B-coexpressed genes were primarily related to the transmembrane transport function and the ubiquitin-mediated proteolysis signaling pathway. As a TF, YY1 might bind to the KDM5B promoter region to regulate KDM5B expression. In addition, miR-29a-3p might bind to and negatively regulate KDM5B expression. SignificanceOur results demonstrate that KDM5B expression is regulated via CNV amplification, DNA hypomethylation, and YY1 and miR-29a-3p; KDM5B expression regulation is associated with patient survival and tumor cell proliferation.

Cytoplasmic localization of connexin 26 suppresses transition of β-catenin into the nucleus in intestinal- and mix-type gastric cancer.

BackgroundConnexin is a basic molecule that forms gap junctions and undergoes localization changes to the cytoplasm in association with carcinogenesis. We aimed to investigate and clarify the significance of cytoplasmic Cx26 expression in gastric cancer.MethodsWe included 87 patients with intestinal‐ and mix‐type gastric cancer and 111 patients with diffuse type gastric cancer who underwent surgery for gastric cancer between 1999 and 2006. Immunohistochemical staining for Cx26, β‐catenin, and Wnt3a was performed and analyses of the relationship to clinicopathological factors were conducted based on the Lauren classification. In an in vitro study, the gastric cancer cell lines MKN7, MKN74, and MKN45 were used to evaluate the proliferative capacity using the water‐soluble tetrazolium salt assay through forced expression of Cx26, and the relationship between Cx26 and β‐catenin was investigated using proximity ligation assay (PLA) and co‐immunoprecipitation. Additionally, functional analysis was performed by Cage analysis.ResultsIn this study, high cytoplasmic Cx26 expression was associated with favorable prognosis in intestinal‐ and mix‐type gastric cancer and could be an independent prognostic factor for overall survival. In terms of the mechanism, in in vitro experiments changes in Cx26 localization to the cytoplasm were shown to suppress the change of localization of β‐catenin to the nucleus by binding to it in the cytoplasm.ConclusionsCytoplasmic Cx26 was found to be a prognostic factor in intestinal‐ and mix‐type gastric cancer. Regarding the mechanism, in vitro studies revealed that cytoplasmic Cx26 inhibits the translocation of β‐catenin to the nucleus.

Inhibition of Musashi-1 enhances chemotherapeutic sensitivity in gastric cancer patient-derived xenografts.

Musashi-1 (MSI1), a neural RNA-binding protein, is considered a gastric and intestinal stem cell marker. Although the function of MSI1 in gastric cancer has attracted increasing interest, it is not known whether MSI1 can be used as a biomarker to monitor gastric cancer development and response to treatment. Here, the role of MSI1 in the chemotherapeutic sensitivity of gastric cancer was investigated. Patients with high MSI1 levels had poor outcomes, implicating the gene in the development and progression of the disease. We overexpressed and silenced MSI1 in the human gastric cancer cell lines MKN45 and HGC27, finding that knockdown reduced proliferation, invasion, and migration, while promoting apoptosis. A patient-derived xenograft gastric cancer model was constructed in which mice received chemical drugs, si-MSI1, or a drug-si-MSI1 combination. It was found that blocking MSI1 expression reduced gastric cancer drug tolerance. The combination treatment with si-MSI1 was superior to 5F-dUMP and cisplatin, either separately or in combination, indicating that including si-MSI1 was better than drug therapy alone. Transcriptome sequencing analysis showed that MSI1 altered cell cycle regulation and growth signal transduction, including that of blood vessel epicardial substance (BVES). These results suggest that MSI1 reduces the tolerance of gastric cancer to chemical drugs through modulation of MSI1/BVES signaling.

Novel 4-phenoxypyridine derivatives bearing imidazole-4-carboxamide and 1,2,4-triazole-3-carboxamide moieties: Design, synthesis and biological evaluation as potent antitumor agents

Two series of novel 4-phenoxypyridine derivatives containing imidazole-4-carboxamide and 4-methyl-5-oxo-4,5-dihydro-1,2,4-triazole-3-carboxamide moieties were synthesized and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against MKN-45, A549 and H460 cancer cell lines. The results indicated that most of the compounds showed moderate to good antitumor activities. The most promising compound T14 (with c-Met IC50 value of 0.012 μM) showed remarkable antiproliferative activities against MKN-45, A549 and H460 cell lines with IC50 values of 0.64 μM, 1.92 μM and 2.68 μM, respectively. Their preliminary structure-activity relationships (SARs) studies indicate that imidazole-4-carboxamide was more preferred as linker part, and electron-withdrawing groups (especially halogen groups) on the terminal phenyl rings were beneficial for improving the antitumor activities.

A Decrease in CD44 on Cell Surfaces (MKN-45 cell line) After RELA Knockout Using CRISPR/Cas9.

The NF-kB signaling pathway was introduced as a key pathway in carcinogenesis that is induced by inflammation in gastrointestinal malignancies. The RelA transcription factor is an important component of this signaling pathway. Furthermore, CD44 is implicated in the tumorigenesis and metastasis of gastric cancer. The aim of this study was to assay the effect of RELA knockout on CD44 expression in MKN45 cells. CRISPR/Cas9 was used to knock out RELA in MKN-45. The medianfluorescence intensity (MFI) of CD44 before and after RELA knockout is analyzed in MKN45. The CRISPR/Cas9 vector pSpCas9 (BB)-2A-Puro (PX459) was used for gRNA cloning (two guides). The MKN-45 cell line was co-transfected. The purified co-transfected cells with puromycin were cultured and used for the RELA gene expression assay by real-time PCR. Flow cytometry was used for the analysis of the MFI of CD44+ in MKN45. The results showed that 180 nucleotide sequences between exon 2 and exon 3 of RELA were deleted in MKN45. RELA expression significantly (P<0.001) decreased after CRISPR/Cas9 knockout. Compared to the control group, the MFI of CD44 in transfected cells significantly decreased (P <0.001). Knockout of RELA significantly decreased CD44 expression in MKN45 cells. It can be concluded that the NF-kB signaling pathway via RELA is related to CD44 expression and consequently the tumorigenesis of gastric cancer. More studies about this relationship are recommended.

Copper nanoparticles supported on polyethylene glycol-modified magnetic Fe3O4 nanoparticles: Its anti-human gastric cancer investigation

In that work, we have described the synthesis of novel Cu NPs decorated polyethylene glycol (PEG 2000 ) coated magnetic nanoparticles (Fe 3 O 4 /PEG2000/Cu NPs) in an eco-friendly pathway applying Green Tea extract as reducing/stabilizing agent. The morphological and physicochemical features of the prepared nanocomposite were determined using several advanced techniques like ICP-OES, FE-SEM, EDX, atomic mapping, TEM, VSM, and XRD studies. In the antioxidant test, the IC50 of Fe 3 O 4 /PEG 2000 /Cu nanocomposite and BHT against DPPH free radicals were 198 and 85 µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with Fe 3 O 4 /PEG 2000 /Cu nanocomposite were assessed by MTT assay for 48 h about the cytotoxicity and anti-human gastric cancer properties on normal (HUVEC) and gastric cancer cell lines i.e. NCI-N87 and MKN45. The IC50 of Fe 3 O 4 /PEG 2000 /Cu nanocomposite were 316 and 131 µg/mL against NCI-N87 and MKN45 cell lines, respectively. The viability of malignant gastric cell line reduced dose-dependently in the presence of Fe 3 O 4 /PEG 2000 /Cu nanocomposite. It seems that the anti-human gastric cancer effect of recent nanoparticles is due to their antioxidant effects.

Evaluation of [18F]tetrafluoroborate as a Potential PET Imaging Agent in a Sodium Iodide Symporter-Transfected Cell Line A549 and Endogenous NIS-Expressing Cell Lines MKN45 and K1.

[18F]tetrafluoroborate (TFB) has been introduced as the 18F-labeled PET imaging probe for the human sodium iodide symporter (NIS). Noninvasive NIS imaging using [18F]TFB has received much interest in recent years for evaluating various NIS-expressing tumors. Cancers are a global concern with enormous implications; therefore, improving diagnostic methods for accurate detection of cancer is extremely important. Our aim was to investigate the PET imaging capabilities of [18F]TFB in NIS-transfected lung cell line A549 and endogenous NIS-expressing tumor cells, such as thyroid cancer K1 and gastric cancer MKN45, and broaden its application in the medical field. Western blot and flow cytometry were used to assess the NIS expression level. Radioactivity counts of [18F]TFB, in vitro, in the three tumor cells were substantially higher than those in the KI inhibition group in the uptake experiment. In vivo PET imaging clearly delineated the three tumors based on the specific accumulation of [18F]TFB in a mouse model. Ex vivo biodistribution investigation showed high [18F]TFB absorption in the tumor location, which was consistent with the PET imaging results. These results support the use of NIS-transfected lung cell line A549 and NIS-expressing tumor cells MKN45 and K1, to investigate probing capabilities of [18F]TFB. We also demonstrate, for the first time, the feasibility of [18F]TFB in diagnosing stomach cancer. In conclusion, this study illustrates the promising future of [18F]TFB for tumor diagnosis and NIS reporter imaging.

Preparation of nanoliposomes loaded with anthocyanins from grape skin extracts: stability, gastric absorption and antiproliferative properties.

Anthocyanin nanoliposomes (ANLs) were produced by a thin film ultrasonic dispersion method to improve the stability and bioavailability of anthocyanins (ACNs) obtained from grape skin extracts. The preparation parameters were predicted to be a soy lecithin to cholesterol ratio of 80 : 19 (w/w, 2 mg of ACNs) under ultrasonication at 120 W for 3.12 min by the response surface methodology. Under the optimal conditions, the fabricated ANLs presented an encapsulation efficiency of 40.1% with an average particle size of 117 nm, a PDI of 0.254 and a ζ-potential of 8.56 mV. The stability of ACNs was improved by nanoliposome encapsulation under various temperature and light conditions. Moreover, a MKN-28 (stomach) barrier model was established to evaluate the cellular transport of ACNs before and after nanoliposome encapsulation. HPLC-DAD/MS analyses demonstrated that ACNs obtained from grape skin extracts mainly consisted of five monomers. After 180 min of transportation, peonidin-3-5-diglucoside and malvidin-3-5-diglucoside (two representative monomers) present in ANLs (0.5 mg mL-1) showed the maximum transport efficiencies of 17.25 ± 1.62% and 18.94 ± 1.05%, respectively. However, their maximum transport efficiencies were 11.68 ± 1.01% and 15.33 ± 1.24%, respectively, existing in ACNs (non-encapsulated form, 0.5 mg mL-1). Furthermore, the antiproliferative properties of ANLs were assessed in two cancer cell lines MKN-28 and HepG-2 (liver). The ANLs presented more effective antiproliferative effects towards MKN-28 than the HepG-2 cell line. This study provides theories and a practice foundation for further application of ACNs as nutraceutical and functional foods.

HOTAIR Induces the Downregulation of miR-200 Family Members in Gastric Cancer Cell Lines

Background:Gastric cancer is the fourth most common human malignancy and the second reason for cancer morbidity worldwide. LncRNA HOTAIR has recently emerged as a promoter of metastasis in various cancer types, including GC, through the EMT process. However, the exact mechanism of HOTAIR in promoting EMT is unknown. Aberrant expression of the miR-200 family has been linked to the occurrence and development of various types of malignant tumors. This study investigates the correlation between the HOTAIR and miR-200 family gene expression patterns in GC cell lines. We investigated the miR-200 and HOTAIR due to their common molecular features in the EMT process. Methods:AGS and MKN45 cell lines were transfected with si-HOTAIR, along with a negative control. The effect of HOTAIR knockdown was also analyzed on cell viability and also on the expression of miR-200 family members, including miR-200a, -200b, and -200c, in cell lines using qRT-PCR. Statistical analysis was performed to find the potential correlation between the expression level of HOTAIR and miRs. Results:Our results showed significant increased miR-200 family expression level in transfected AGS and MKN45 GC cells (fold changes > 2; p < 0.001). Moreover, a negative correlation was observed between HOTAIR and miR-200 expression levels in GC cell lines (p < 0.05). Conclusion:Our findings showed a significant association between miR-200 family and HOTAIR expression levels in GC cell lines. Taken together, the HOTAIR-miR-200 axis seems to play a vital role in human GC, suggesting a potential therapeutic target in future GC treatment.