Gastric Adenocarcinoma Cell Line Research Articles

Exploring the immune escape mechanisms in gastric cancer patients based on the deep AI algorithms and single-cell sequencing analysis.

Gastric cancer is a prevalent and deadly malignancy, and the response to immunotherapy varies among patients. This study aimed to develop a prognostic model for gastric cancer patients and investigate immune escape mechanisms using deep machine learning and single-cell sequencing analysis. Data from public databases were analysed, and a prediction model was constructed using 101 algorithms. The high-AIDPS group, characterized by increased AIDPS expression, exhibited worse survival, genomic variations and immune cell infiltration. These patients also showed immunotherapy tolerance. Treatment strategies targeting the high-AIDPS group identified three potential drugs. Additionally, distinct cluster groups and upregulated AIDPS-associated genes were observed in gastric adenocarcinoma cell lines. Inhibition of GHRL expression suppressed cancer cell activity, inhibited M2 polarization in macrophages and reduced invasiveness. Overall, AIDPS plays a critical role in gastric cancer prognosis, genomic variations, immune cell infiltration and immunotherapy response, and targeting GHRL expression holds promise for personalized treatment. These findings contribute to improved clinical management in gastric cancer.

Circular RNA hsa_circ_0094976 modulates GPR155 to inhibit gastric adenocarcinoma malignant characteristics by targeting miR-223–3p

BackgroundThe abnormal expression of circular RNA (circRNA) has been confirmed to be closely related to the development of many human diseases including gastric adenocarcinoma (GA). This study aimed to elucidate the molecular mechanism and biological function of hsa_circ_0094976 (circ_0094976) in GA. MethodsThe expression of circ_0094976, miR-223–3p, and G protein-coupled receptor 155 (GPR155) mRNA was measured by quantitative real-time polymerase chain reaction. Cell viability, cell proliferation, colony formation, migration, and invasion were estimated by cell counting kit-8 assay, 5-Ethynyl-2’-deoxyuridine assay, colony formation assay, and transwell assay, respectively. The bioinformatics analysis, dual-luciferase reporter assay, and RNA pull-down assay were used for predicting and verifying the interaction of the circ_0094976/miR-223–3p/GPR155 axis. A xenograft mouse model was performed in nude mice to reveal the role of circ_0094976 in vivo. ResultsCirc_0094976 was down-regulated in GA tissues and GA cell lines compared to normal controls. Overexpression of circ_0094976 inhibited the GA cell growth, migration, and invasion in vitro, and tumor growth in vivo. Circ_0094976 directly targeted miR-223–3p, and GPR155 was a direct target of miR-223–3p. Moreover, circ_0094976 sponging miR-223–3p to increase the expression of GPR155. ConclusionWe disclosed that circ_0094976 could act as a sponge of miR-223–3p to regulate the expression of GPR155, and further restrain the development of GA, which may provide new insight into the therapy of GA.

Discovery of YS-1 as a cell line of gastric inflammatory cancer-associated fibroblasts.

Inflammatory cancer-associated fibroblasts (iCAFs) was first identified by co-culture of pancreatic stellate cells and tumor organoids. The key feature of iCAFs is IL-6high/αSMAlow. We examine this phenomenon in gastric cancer using two cell lines of gastric fibroblasts (HGF and YS-1). HGF or YS-1 were co-cultured with MKN7 (a gastric adenocarcinoma cell line) in Matrigel. IL-6 protein levels in the culture supernatant were measured by ELISA. The increased production of IL-6 was not observed in any of the combinations. Instead, the supernatant of YS-1 exhibited the higher levels of IL-6. YS-1 showed IL-6high/αSMA (ACTA2)low in real-time PCR, mRNA-seq and immunohistochemistry. In mRNA-seq, iCAFs-associated genes and signaling pathways were up-regulated in YS-1. No transition to myofibroblastic phenotype was observed by monolayer culture, or the exposure to sonic hedgehog (SHH) or TGF-β. YS-1 conditioned medium induced changes of morphology and stem-ness/differentiation in NUGC-3 (a human gastric adenocarcinoma cell line) and UBE6T-15 (a human bone marrow-derived mesenchymal stem cell line). YS-1 is a stable cell line of gastric iCAFs. This discovery will promote further research on iCAFs for many researchers.

68Ga-NC-BCH Whole-Body PET Imaging Rapidly Targets Claudin18.2 in Lesions in Gastrointestinal Cancer Patients.

68Ga-labeled nanobody (68Ga-NC-BCH) is a single-domain antibody-based PET imaging agent. We conducted a first-in-humans study of 68Ga-NC-BCH for PET to determine its invivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying claudin-18 isoform 2 (CLDN18.2) expression in gastrointestinal cancer patients. Methods: Initially, we synthesized the probe 68Ga-NC-BCH and performed preclinical evaluations on human gastric adenocarcinoma cell lines and xenograft mouse models. Next, we performed a translational study with a pilot cohort of patients with advanced gastrointestinal cancer on a total-body PET/CT scanner. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship between tumor uptake and CLDN18.2 expression were evaluated. Results: 68Ga-NC-BCH was stably prepared and demonstrated good radiochemical properties. According to preclinical evaluation,68Ga-NC-BCH exhibited rapid blood clearance, high affinity for CLDN18.2, and high specific uptake in CLDN18.2-positive cells and xenograft mouse models. 68Ga-NC-BCH displayed high uptake in the stomach and kidney and slight uptake in the pancreas. Compared with 18F-FDG, 68Ga-NC-BCH showed significant differences in uptake in lesions with different levels of CLDN18.2 expression. Conclusion: A clear correlation was detected between PET SUV and CLDN18.2 expression, suggesting that 68Ga-NC-BCH PET could be used as a companion diagnostic tool for optimizing treatments that target CLDN18.2 in tumors.

The effect of 1-deoxynojirimycin isolated from logging residue of Bagassa guianensis on an in vitro cancer model

Introduction:Bagassa guianensis Aubl, a tree widely distributed in Brazil, significantly contributes to the furniture industry. Notably, it harbors the bioactive compound 1-deoxynojirimycin (1-DNJ), which is retrievable from timber residues and retains activity even days after wood extraction. This makes Bagassa guianensis a promising biological resource for anticancer therapy and pharmacology studies. This study delves into the in vitro antineoplastic actions of 1-DNJ, focusing on adenocarcinoma gastric cell lines (ACP02) and glioblastoma (A172).Methods: The effect of 1-DNJ on cell viability was evaluated after 72 hours of treatment in the ACP02 and A172 cell lines. We also assessed the effect of 1-DNJ on the pattern of cell migration, cell death, changes in the cell cycle by flow cytometry, the production of reactive oxygen, and its antioxidant capacity in the scavenging of free radicals.Results: Assessing cell viability after 72 h (about 3 days) of treatment reveals a remarkable reduction, particularly in glioblastoma cells (A172), exhibiting a lower IC50 compared to ACP02 and MRC5 (fibroblast derived from normal lung tissue) cell lines. This decreased viability correlates with reduced reactive oxygen species (ROS) production in both cell lines after the treatment with 1-DNJ. Furthermore, 1-DNJ induces cell cycle arrest, impedes cell migration, and prompts cell death in ACP02 and A172.Discussion: These findings support 1-DNJ as a potent antineoplastic agent, particularly efficacious against glioblastoma and gastric adenocarcinoma. Thus, unveiling the therapeutic potential of Bagassa guianensis Aubl for cancer treatment and expanding the horizons of bioeconomy applications.

Pyrazole-based and N,N-diethylcarbamate functionalized some novel aurone analogs: Design, synthesis, cytotoxic evaluation, docking and SAR studies, against AGS cancer cell line

The present study involves the design, synthesis, and biological evaluation of a series of thirty-three, pyrazole-based and N,N-diethylcarbamate functionalized, novel aurone analogs, against AGS cancer cell line. These novel aurone analogs are obtained from the reaction of pyrazole-based 6-hydroxyaurones with diethyl carbamoyl chloride using mild basic reagent. The cytotoxic activities of these compounds were evaluated against a human gastric adenocarcinoma cell line (AGS) and disclosed some potential outcomes as several analogs were found to have cytotoxicity better than the reference drugs Oxaliplatin and Leucovorin. The structure-activity relationship (SAR) study further unveiled the critical role of replacing the hydroxyl group in ring A with a carbamoyl group for cytotoxic activity. Among these aurone analogs, 8e and 8f, with IC50 values of 6.5 ± 0.024 μM and 6.6 ± 0.035 μM, respectively, are identified as the most active compounds. Molecular docking studies were conducted against HER2, a human epidermal growth factor involved in gastric and ovarian cancer, to investigate the binding interactions between the compounds and the protein HER2, where7e and 8e exhibited maximum interactions.

Synthesis, in silico studies, and in vitro biological evaluation of newly-designed 5-amino-1H-tetrazole-linked 5-fluorouracil analog as a potential antigastric-cancer agent

5-Fluorouracil (5FU) is a chemotherapy drug used to treat various cancers, such as colorectal, prostate, skin, pancreas, and stomach, as an ointment or solution. However, its consumption has several side effects. Therefore, a new derivative of fluorouracil containing 5-Amino-1H-tetrazole was designed and synthesized through multi-step synthesis to reduce urea excretion and toxicity. The effectiveness of the synthesized drug on the Adenocarcinoma gastric cell line (AGS) gastric cancer cell line was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, which showed that the new 5-fluorouracil (5FU) analog, with an IC50 of 15.67 µg/mL, is more effective in inhibiting the proliferation of AGS cells after 24 h compared to both synthesized and reported 5FU. In addition, In-silico studies showed that the new 5FU derivative based on amino tetrazole, with a binding energy of −7.2 kcal/mol, exhibits greater anti-cancer activity against the BCL2 enzyme than 5FU, with a binding energy of − 4.8 kcal/mol. It is predicted that the new 5FU derivative will be effective in treating gastric and colorectal cancers. The new derivative of the 5-fluorouracil drug was characterized and identified using FTIR and NMR spectroscopy. Communicated by Ramaswamy H. Sarma

The inhibition effects of Lentilactobacillus buchneri-derived membrane vesicles on AGS and HT-29 cancer cells by inducing cell apoptosis

In recent years, probiotics and their derivatives have been recognized as important therapeutic agents in the fight against cancer. Therefore, this study aimed to investigate the anticancer effects of membrane vesicles (MVs) from Lentilactobacillus buchneri strain HBUM07105 probiotic isolated from conventional and unprocessed yogurt in Arak province, Iran, against gastric and colon cancer cell lines. The MVs were prepared from the cell-free supernatant (CFS) of L. buchneri and characterized using field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) and SPS-PAGE techniques. The anticancer activity of MVs was evaluated using MTT, flow cytometry, qRT-PCR techniques, and a scratch assay. The study investigated the anti-adenocarcinoma effect of MVs isolated from L. buchneri on a human gastric adenocarcinoma cell line (AGS) and a human colorectal adenocarcinoma cell line (HT-29) at 24, 48, and 72-h time intervals. The results demonstrated that all prepared concentrations (12.5, 25, 50, 100, and 200 µg/mL) of MVs reduced the viability of both types of human adenocarcinoma cells after 24, 48, and 72 h of treatment. The analysis of the apoptosis results revealed that the percentage of AGS and HT-29 cancer cells in the early and late stages of apoptosis was significantly higher after 24, 48, and 72 h of treatment compared to the untreated cancer cells. After treating both AGS and HT-29 cells with the MVs, the cells were arrested in the G0/G1 phase. These microvesicles demonstrate apoptotic activity by increasing the expression of pro-apoptotic genes (BAX, CASP3, and CASP9). According to the scratch test, MVs can significantly decrease the migration of HT-29 and AGS cancer cells after 24, 48, and 72 h of incubation compared to the control groups. The MVs of L. buchneri can also be considered a potential option for inhibiting cancer cell activities.

An Alternative Green Method for Synthesis of 3-Amino-5-Methylisoxazole Schiff Bases and Their Bioactivity Evaluation

Isoxazole Schiff bases play an important role in medicinal chemistry, pharmacy, coordination chemistry, and industrial chemistry, therefore, finding easier and more reliable procedures for their synthesis is still in process. The present work deals with a single-step condensation reaction between 3-amino-5-methylisoxazole and various aromatic aldehydes to furnish a Schiff base scaffold of isoxazole (including one new compound) with excellent yields in a short time. The procedure is a solvent-free condition using DMEA as a green catalyst. The products were evaluated for their antibacterial efficacy against gram-positive and gram-negative bacteria including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Salmonella abony. The antioxidant activity of the products was tested and the ascorbic acid and quercetin were used as standards. The produced Schiff bases exhibited the ability to scavenge the free radicals from the DPPH. This means that the products can be used as antioxidants. Two of the synthesized compounds were evaluated for their anticancer activity by testing their cytotoxic potency, which showed diminishing toxicity of cell lines against human breast cancer cell lines and gastric adenocarcinoma cell lines. Therefore, the products can be utilized as anticancer agents.

Characterization, Antioxidant and Cytotoxic Evaluation of Demethoxycurcumin and Bisdemethoxycurcumin from Curcuma longa Cultivated in Costa Rica

The biological activities of curcuminoids, the main polyphenol constituents of Curcuma longa (turmeric), have been the subject of many studies in recent years. However, these studies have focused on the major active compound, curcumin (CUR), while other important constituents, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDM) have been less studied and reported in the literature regarding their bioactivity as well as their isolation and solid-state characterization. Hence, in this study, DMC and BDM were isolated using pressurized liquid extraction (PLE) followed by column chromatography and crystallization. HRMS and 1H and 13C NMR were used to characterize them. Solid-state characterization was performed through powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) techniques. Further, powder dissolution profiles were performed in two media, antioxidant and cytotoxic activities were determined through 2,2-diphenyl-1-picrylhidrazyl (DPPH) and an MTT assay on gastric adenocarcinoma (AGS), colorectal adenocarcinoma (SW-620), and hepatocellular carcinoma (HepG2) cell lines. DMC and BDM were extracted from Curcuma longa cultivated in Costa Rica, using pressurized liquid extraction (PLE), then isolated and purified, combining column chromatography and crystallization techniques. The highly pure solids obtained were shown to be crystalline with an amorphous component. Although the PXRD pattern of BDM suggested a high amorphous component, the crystal exhibited a well-defined and faceted shape. Meanwhile, DMC crystallized in a botryoidal habit, and this constitutes the first report for this compound. On the other hand, BDM was slightly more soluble than DMC, which in turn showed an antioxidant IC50 value 28% higher than BDM (12.46 and 17.94 µg/mL, respectively). In respect to the cytotoxic effects, DMC showed a better IC50 value than BDM for both the SW-620 and AGS cell lines, while BDM exhibited a better IC50 value than DMC against the HepG2 cell line (64.7 μM). In terms of selectivity, BDM and DMC had the highest SI value for SW-620 cells compared to non-tumoral cells, while both compounds also displayed the best cytotoxic effect against these colon adenocarcinoma SW-620 cells, indicating BDM and DMC as potential chemotherapeutic drugs.

A pH-Sensitive Fluorescent Chemosensor Turn-On Based in a Salen Iron (III) Complex: Synthesis, Photophysical Properties, and Live-Cell Imaging Application.

pH regulation is essential to allow normal cell function, and their imbalance is associated with different pathologic situations, including cancer. In this study, we present the synthesis of 2-(((2-aminoethyl)imino)methyl)phenol (HL1) and the iron (III) complex (Fe(L1)2Br, (C1)), confirmed by X-ray diffraction analysis. The absorption and emission properties of complex C1 were assessed in the presence and absence of different physiologically relevant analytes, finding a fluorescent turn-on when OH- was added. So, we determined the limit of detection (LOD = 3.97 × 10-9 M), stoichiometry (1:1), and association constant (Kas = 5.86 × 103 M-1). Using DFT calculations, we proposed a spontaneous decomposition mechanism for C1. After characterization, complex C1 was evaluated as an intracellular pH chemosensor on the human primary gastric adenocarcinoma (AGS) and non-tumoral gastric epithelia (GES-1) cell lines, finding fluorescent signal activation in the latter when compared to AGS cells due to the lower intracellular pH of AGS cells caused by the increased metabolic rate. However, when complex C1 was used on metastatic cancer cell lines (MKN-45 and MKN-74), a fluorescent turn-on was observed in both cell lines because the intracellular lactate amount increased. Our results could provide insights about the application of complex C1 as a metabolic probe to be used in cancer cell imaging.

Heterogeneous Cellular Response of Primary and Metastatic Human Gastric Adenocarcinoma Cell Lines to Magnoflorine and Its Additive Interaction with Docetaxel

Gastric cancer is the most common cancer and remains the leading cause of cancer death worldwide. In this study, the anticancer action of magnoflorine isolated via counter-current chromatography from the methanolic extract of Berberis vulgaris root against gastric cancer in models of primary ACC-201 and AGS and metastatic MKN-74 and NCI-N87 cell lines was analyzed. Cell viability and proliferation were tested through the use of MTT and BrdU tests, respectively. Cell cycle progression and apoptosis were evaluated using flow cytometry. The interaction of magnoflorine and docetaxel has been examined through isobolographic analysis. Moreover, potential toxicity was verified in zebrafish in an in vivo model. Gastric cancer cell lines revealed different responses to magnoflorine treatment with regard to viability/proliferation, apoptosis induction and cell cycle inhibition without any undesirable changes in the development of larval zebrafish at the tested concentrations. What is more, magnoflorine in combination with docetaxel produced an additive pharmacological interaction in all studied gastric cancer cell lines, which may suggest a complementary mechanism of action of both compounds. Taken together, these findings provide a foundation for the possibility of magnoflorine as a potential therapeutic approach for gastric cancer and merits further investigation, which may pave the way for clinical uses of magnoflorine.

Novel biogenic preparation of gold nanoparticles decorated on sepiolite clay and evaluation of anti-cancer effect on gastric cancer cell and electrochemical sensing of nitrite

An environmentally friendly strategy was used in this study to synthesize gold nanoparticles decorated on sepiolite clay (GNPs-SC) using Heracleum persicum grass extract. The physicochemical characters of the prepared composite were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). A GNPs-SC modified carbon pate electrode (CPE) was used to study the electrochemical oxidation of nitrite. The proposed nitrite sensor exhibits excellent performance, including a broad linear range (1.0–150 μM), a low limit of detection (0.4 μM), and acceptable reproducibility (RSD = 2.6%). As well, the prepared GNPs-SC was tested for its effectiveness against human gastric adenocarcinoma (AGS) cell line. The MTT assay protocol revealed that the bio-synthesized product displayed significant cytotoxic activity against gastric cancer in human subjects. The findings of this study indicate that GNPs-SC, synthesized using environmentally friendly protocol, exhibit great potential for use in electrochemical sensing and treatment of human cancer.

Binding of YY1/CREB to an Enhancer Region Triggers Claudin 6 Expression in H. pylori LPS-Stimulated AGS Cells.

Aberrant expression of the tight junction protein claudin 6 (CLDN6) is a hallmark of gastric cancer progression. Its expression is regulated by the cAMP response element-binding protein (CREB). In gastric cancer induced by Helicobacter pylori (H. pylori) there is no information regarding what transcription factors induce/upregulate the expression of CLDN6. We aimed to identify whether CREB and Yin Yang1 (YY1) regulate the expression of CLDN6 and the site where they bind to the promoter sequence. Bioinformatics analysis, H. pylori lipopolysaccharide (LPS), YY1 and CREB silencing, Western blot, luciferase assays, and chromatin immunoprecipitation experiments were performed using the stomach gastric adenocarcinoma cell line AGS. A gen reporter assay suggested that the initial 2000 bp contains the regulatory sequence associated with CLDN6 transcription; the luciferase assay demonstrated three different regions with transcriptional activity, but the -901 to -1421 bp region displayed the maximal transcriptional activity in response to LPS. Fragment 1279-1421 showed CREB and, surprisingly, YY1 occupancy. Sequential Chromatin Immunoprecipitation (ChIP) experiments confirmed that YY1 and CREB interact in the 1279-1421 region. Our results suggest that CLDN6 expression is regulated by the binding of YY1 and CREB in the 901-1421 enhancer, in which a non-described interaction of YY1 with CREB was established in the 1279-1421 region.

Cytotoxic effect of NiFe2O4@Ag nanoparticle on adenocarcinoma gastric cell line (AGS) and assessment of the expression of CASP8, BAX, NRF2, and BCL2 genes

In this research, the researchers evaluated the apoptotic property of NiFe2O4@Ag nanoparticle biosynthesized by Chlorella vulgaris on adenocarcinoma gastric cell line (AGS). The specification of synthesized NiFe2O4@Ag nanoparticles was investigated via several analytical analyses including, SEM (Scanning Electron Microscopy), TEM (Transmission Electron Microscopy), FTIR (Fourier Transform Infrared Spectroscopy), EDX (Energy Dispersive X-ray), Zeta potential analysis, DLS (Dynamic Light Scattering) and XRD (X-Ray Diffraction). To evaluate the in vitro cytotoxic effect, the AGS cells (cancer line) and HEK293 cells (normal cell line) were treated with different concentrations of NiFe2O4@Ag nanoparticles by MTT test. Moreover, the apoptogenic impact of the nanoparticles was assessed using Hoechst staining, annexin V- Fluorescein isothiocyanate (FITC) and propidium iodide (PI) staining, and Caspase 3 activity assay. Microscopic inspections of nanoparticles showed rounded shape and small particles in a size range of 30 to 60 nm. The MTT test indicated that the nanoparticles caused a dose-dependent inhibition of AGS cells (IC50 = 122.57 μg/mL). According to the Annexin V/PI staining assay, an increase in the frequency of apoptotic cells (51.75 %) in comparison to control cells was found. Based on the Caspase3 activity assay, nanoparticles led to an increase in Caspase3 level by 3.1 folds. Investigation of ROS (Reactive Oxygen Species) production exhibited that the nanoparticles can exert toxicity through an increase in ROS level. Cell cycle analysis confirmed an increase in the number of the cells in Sub-G1 step among nanoparticles treated cells. Furthermore, the expression of the BAX and CASP8 genes increased by 2.6 and 3.7 folds, respectively, whereas the BCL-2 gene was downregulated by 0.85 folds. Moreover, Hoechst staining indicated in vitro anti-tumor effect of the nanoparticles by appearance of apoptotic symptoms in AGS cells. Our results showed that NiFe2O4@Ag nanoparticled could efficiently cause the obstruction of AGS cell proliferation and apoptosis induction.

ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1.

Adenosine deaminases acting on RNA1 (ADAR1) are involved in the occurrence and development of cancers. Although the role of ADAR1 in gastric cancer metastasis has been reported, the role of ADAR1 in the mechanism of cisplatin resistance in gastric cancer is not clear. In this study, human gastric cancer tissue specimens were used to construct cisplatin-resistant gastric cancer cells; the results indicated that the mechanism underlying the inhibition of gastric cancer metastasis and reversal of cisplatin-resistant gastric cancer by ADAR1 inhibits gastric cancer occurs through the antizyme inhibitor 1 (AZIN1) pathway. We assessed ADAR1 and AZIN1 expression in the tissues of patients with low to moderately differentiated gastric cancer. Gastric cancer cells (human gastric adenocarcinoma cell line [AGS] and HGC-27 cells) and gastric cancer cisplatin-resistant cells (AGS CDDP and HGC-27 CDDP ) were selected, and the protein expression of ADAR1 and AZIN1 was detected using immunocytochemistry and immunocytofluorescence. The effects of ADAR1 small interfering RNA (siRNA) on the invasion, migration and proliferation of cisplatin-resistant gastric cancer cells were investigated. Western blot assays were used to assess the protein expression levels of ADAR1, AZIN1 and epithelial-mesenchymal transition (EMT)-related markers. In-vivo experiments, a subcutaneous tumor formation model of nude mice was established, and the effects of ADAR1 on tumor growth and AZIN1 expression level were detected by hematoxylin and eosin, immunohistochemistry and western blot. The expression of ADAR1 and AZIN1 in human gastric cancer tissue was significantly higher than that in paracancerous tissues. The colocalization of ADAR1, AZIN1 and E-cadherin expression in immunofluorescence assays indicated a significant correlation between the three. In in-vitro experiments, ADAR1 knockout not only reduced the invasion and migration ability of AGS and HGC-27 cells but also reduced that of cisplatin-resistant gastric cancer cells. ADAR1 siRNA inhibited the proliferation and decreased the colony number of cisplatin-resistant gastric cancer cells. ADAR1 siRNA decreased the expression of AZIN1 and EMT-related marker proteins (vimentin, N-cadherin, β-catenin, MMP9, MMP2 and TWIST). The effect of ADAR1 siRNA combined with AZIN1 siRNA was more significant. In-vivo, the knockdown of ADAR1 significantly inhibited tumor growth and AZIN1 expression. ADAR1 and AZIN1 are antimetastatic targets of gastric cancer, and AZIN1 is a downstream regulatory target of ADAR1. ADAR1 knockout can inhibit the metastasis of gastric cancer cells and reverse the cisplatin resistance of gastric cancer cells by downregulating the expression of AZIN1, potentially resulting in increased treatment efficacy.

Effects of Probiotic Saccharomyces boulardii Supernatant on Viability, Nano-Mechanical Properties of Cytoplasmic Membrane and Pro-Inflammatory Gene Expression in Human Gastric Cancer AGS Cells.

Gastric cancer has been recognized as the second most probable cause of death in humans from cancer diseases around the world. Postbiotics, supernatant, and metabolites from probiotic microorganisms have recently been used widely to prevent and treat cancer diseases in humans, without any undesirable side effects. This study explores the antiproliferative and antitumor activities of the probiotic Saccharomyces cerevisiae var. boulardii supernatant (SBS) against AGS cancer cells, a human gastric adenocarcinoma cell line. We evaluated cell growth inhibitory and mechanical properties of the cytoplasmic membrane and the downregulation of survivin and proinflammatory genes in AGS cells treated with SBS after 24 and 48 h. SBS significantly inhibits the AGS cell growth, and the concentrations with IC50 values after 24 and 48 h treatments are measured as 2266 and 1956 µg/mL, respectively. Regarding the AFM images and Young`s modulus analysis, SBS significantly induces morphological changes in the cytoplasmic membrane of the treated AGS cells. Expression of survivin, NFƙB, and IL-8 genes is significantly suppressed in AGS cells treated with SBS. Considering the antitumor activities of SBS on AGS cell line, it can be regarded as a prospective therapeutic and preventive strategy against human stomach cancer disease.

Inhibitory and anti-Cancer Effects of Crataegus azarolus Extracts on Gastric Cancer Cell Line (AGS)

Gastric cancer (GC) is one of the most frequent types of cancer around the world and most of the drugs which are used currently as anti-cancer chemotherapy hold adverse side effects on normal cells and tissues, that calls for a strong need to find new agents to prevent and treat GC. Extracts from certain plants contain compounds with health potentials with minimal side effects; one such plant is the Crataegus azarolus commonly called hawthorn. Extracts of hawthorn have been found to exert negative effects on the viability of many types of cancer via a number of pathways both in vivo and in vitro. Herein, we aimed to investigate the possible anti-proliferative effects of methanolic and acetone extracts of C. azarolus leaves on human adenocarcinoma gastric cell line (AGS). Standard phytochemical analysis were used to qualitatively characterize leaf extracts contents. AGS cells were treated for 48 h with different concentrations of both extracts (10, 50, 100, 250, and 500 µg/ml). Our results demonstrated that the methanolic crude extract showed significantly higher anti-proliferative effects than those of acetone, at both 250 and 500 µg/ml concentrations respectively, when estimated by MTT assay at (p< 0.001) with an IC50 values 293.7 µg/ml. On the other hand, acetone extract treatment showed that 500 µg/ml had a high significant effect at (p< 0.001) with an IC50 values 576.6 µg/ml. In conclusion, the results of the present study indicated that leaf extracts of C. azarolus limited the growth of AGS.

Esophageal cancer-related gene 4 inhibits gastric cancer growth and metastasis by upregulating Krüppel-like factor 2 expression.

There are a large number of people suffering from gastric cancer (GC) worldwide, so the study of biomarkers for GC is urgently needed. This study aimed to investigate the role of esophageal cancer-related gene 4 (ECRG4) in the growth, metastasis, and prognosis of GC and the possible underlying mechanism. The expression of ECRG4 was detected in GC tissues by quantitative polymerase chain reaction (PCR), Western blot, and immunohistochemistry. The relationships between ECRG4 expression and clinicopathological parameters of patients with GC were statistically analyzed, and Kaplan-Meier prognosis and survival curves of the patients were plotted. ECRG4 was overexpressed in the human gastric adenocarcinoma cell line (AGS) and human GC cell line 27 (HGC27), and the in vivo effects of ECRG4 overexpression on the growth, invasion, and metastasis of GC were analyzed and verified in nude mice. To identify the downstream transcription factors potentially regulated by ECRG4, ribonucleic acid (RNA) sequencing and differential gene expression analysis were performed on ECRG4-overexpressing cells. Quantitative PCR, Western blot, and immunohistochemistry were used to detect the expression of the downstream transcription factors targeted by ECRG4 in GC. The ECRG4 mRNA and protein expression levels were low in GC tissues and were associated with a poor prognosis. Least absolute shrinkage and selection operator (LASSO) Cox regression and Kaplan-Meier survival analyses showed that patients with low ECRG4 expression had worse prognosis and survival. Overexpression of ECRG4 inhibited the proliferation, metastasis, and invasion of GC cells. RNA sequencing analysis showed that overexpression of ECRG4 induced the upregulation of Krüppel-like factor 2. Our findings show that ECRG4 promotes GC progression via Krüppel-like factor 2 signaling and highlight ECRG4 as a potential GC biomarker and therapeutic target.

Evaluation of anticancer potential of methanolic leaf and flower extracts of Rhododendron arboreum Sm in AGS gastric adenocarcinoma cell line

Evaluation of anticancer potential of methanolic leaf and flower extracts of Rhododendron arboreum Sm in AGS gastric adenocarcinoma cell line