scholarly journals Famotidine promotes inflammation by triggering cell pyroptosis in gastric cancer cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jin Huang ◽  
Pingsheng Fan ◽  
Miao Liu ◽  
Chengtao Weng ◽  
Gaofei Fan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Swelling ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Histamine H2 Receptor ◽  
Real Time Quantitative Pcr ◽  
Release Assay

Abstract Background Cell pyroptosis has been characterized by cell swelling and pro-inflammatory factors release to aggravate inflammatory reaction., such as interlukin-1 beta (IL-1β) and interlukin18 (IL-18). However, the function of famotidine, an antagonist of histamine H2-receptor antagonists, in cell pyroptosis remained unknown. Methods Real-time quantitative PCR (qPCR), western blotting (WB), LDH release assay and enzyme linked immunosorbent assay (Elisa) combined with inhibitor were performed to analyze the effect of famotidine on cell pyroptosis-related gene expression. Results In this study, we found that famotidine (300 μm) treatment led to a phenomenon of cell pyroptosis as confirmed by LDH assay. Further results showed that famotidine triggered cell pyroptosis in gastric cancer cells by activation of NLPR3 inflammasomes including ASC, Caspase-1 and NLRP, leading to enhanced IL-18, not IL-1β, mature and secretion. What’s more, the results also showed GSDME, not GSDMD, was increased in response to famotidine stimulation in BGC823 and AGS cells. Mechanically, phosphorylation of ERK1/2 was drastically enhanced in present with famotidine treatment, while inhibition of ERK1/2 activity by U0126 could reverse the promotion of famotidine in IL-18 secretion. Conclusion These findings revealed a novel role of famotidine in cell pyroptosis in patients with gastric cancer, a comprehensive consideration is needed in treatment of gastric cancer.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

scholarly journals Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells

2013 ◽  
Vol 42 (5) ◽  
pp. 2988-2998 ◽  
Author(s):  
Xiaoli Tang ◽  
Dong Zheng ◽  
Ping Hu ◽  
Zongyue Zeng ◽  
Ming Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cancer Tissue ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Cell Functions

Abstract Glycogen synthase kinase 3 beta (GSK3β) is a critical protein kinase that phosphorylates numerous proteins in cells and thereby impacts multiple pathways including the β-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of noncoding small RNAs of ∼22 nucleotides in length. Both GSK3β and miR play myriad roles in cell functions including stem cell development, apoptosis, embryogenesis and tumorigenesis. Here we show that GSK3β inhibits the expression of miR-96, miR-182 and miR-183 through the β-Catenin/TCF/LEF-1 pathway. Knockout of GSK3β in mouse embryonic fibroblast cells increases expression of miR-96, miR-182 and miR-183, coinciding with increases in the protein level and nuclear translocation of β-Catenin. In addition, overexpression of β-Catenin enhances the expression of miR-96, miR-182 and miR-183 in human gastric cancer AGS cells. GSK3β protein levels are decreased in human gastric cancer tissue compared with surrounding normal gastric tissue, coinciding with increases of β-Catenin protein, miR-96, miR-182, miR-183 and primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183-96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and migration of AGS cells. Knockdown of GSK3β with siRNA increases the proliferation of AGS cells. Mechanistically, we show that β-Catenin/TCF/LEF-1 binds to the promoter of miR-183-96-182 cluster gene and thereby activates the transcription of the cluster. In summary, our findings identify a novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

scholarly journals Effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of gastric cancer cells

2019 ◽  
Vol 17 ◽  
pp. 205873921984553
Author(s):  
Ying Guo ◽  
Li Zhang ◽  
Guangyu Zhou ◽  
Qingjie Ma ◽  
Shi Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Negative Control ◽  
Control Group ◽  
Gastric Cancer Cells ◽  
Ags Cells

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.

scholarly journals The Complex Toxicity of Tetracycline with Polystyrene Spheres on Gastric Cancer Cells

2020 ◽  
Vol 17 (8) ◽  
pp. 2808 ◽  
Author(s):  
Xiemin Yan ◽  
Yuanyuan Zhang ◽  
Yuqin Lu ◽  
Lei He ◽  
Junhao Qu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Defense Mechanism ◽  
Natural Environments ◽  
Polystyrene Spheres ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Oxidation Stress ◽  
Strong Adsorption

Nowadays, microplastics (MPs) exist widely in the marine. The surface has strong adsorption capacity for antibiotics in natural environments, and the cytotoxicity of complex are poorly understood. In the study, 500 nm polystyrene (PS-MPs) and 60 nm nanoplastics (PS-NPs) were synthesized. The adsorption of PS to tetracycline (TC) was studied and their toxicity to gastric cancer cells (AGS) was researched. The adsorption experimental results show that PS absorbing capacity increased with increasing TC concentrations. The defense mechanism results show that 60 nm PS-NPs, 500 nm PS-MPs and their complex induce different damage to AGS cells. Furthermore, 600 mg/L PS-NPs and PS-MPs decline cell viability, induce oxidation stress and cause apoptosis. There is more serious damage of 60 nm PS-NPs than 500 nm PS-MPs in cell viability and intracellular reactive oxygen species (ROS). DNA are also damaged by 60 nm PS-NPs and PS-TC NPs, 500 nm PS-MPs and PS-TC MPs, and 60 nm PS-NPs damage DNA more serious than 500 nm PS-MPs. Moreover, 60 nm PS-NPs and PS-TC NPs seem to promote bcl-2 associated X protein (Bax) overexpression. All treatments provided us with evidence on how PS-NPs, PS-MPs and their compounds damaged AGS cells.

Effect of trastuzumab on telomere-related proteins and the relationship to the sensitivity of HER2-amplified human gastric cancer cells to oxaliplatin and cisplatin.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 53-53
Author(s):  
Yongping Liu ◽  
Yang Ling ◽  
Qiu feng Qi ◽  
Yaodong Pan
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Annexin V ◽  
Human Gastric Cancer ◽  
Her2 Gene ◽  
Gastric Cancer Cells ◽  
Real Time Quantitative Pcr ◽  
Induced Apoptosis ◽  
Platinum Agents

53 Background: HER2 amplification occurs in about 20% of gastric cancers, and trastuzumab in combination with cisplatin based chemotherapy has been reported to improve oncological outcomes in gastric and gastro-oesophageal junction cancer with HER2 gene amplification. The aim of this study was to evaluate the potentially useful combined antitumor efficacy of trastuzumab and platinum agents in gastric cancer cells and to elucidate further the mechanisms possibly involved in the interaction between the trastuzumab and platinum agents. Methods: Gene expression was determined by using real-time quantitative PCR in gastric cancer cell lines. The chemosensitivity of gastric cancer cells to platinum agents and the apoptotic effect of drugs in vitro were evaluated using cellTiter 96 Aqueous One Solution Cell Proliferation Assay kit and double staining with both Annexin-V-FITC and PI, respectively. Results: Treatment with 1.0μg/ml trastuzumab for 48h could significantly increase sensitivity of oxaliplatin or cisplatin in HER2 amplified gastric cancer cells, and the IC50 of oxaliplatin and cisplatin were reduced to about 3.29 times and 6.91 times, respectively. Apoptosis analysis also indicated that trastuzumab significantly increased both oxaliplatin and cisplatin-induced apoptosis in NCI-N87 cells. Analysis of telomere-related genes revealed that trastuzumab singly and pretreatment with trastuzumab for 48h followed by oxaliplatin or cisplatin for another 48h could significantly downregulate the mRNA expression of TPP1, TRF1, TRF2, TRF2IP, POT1 and TIN2 genes. Conclusions: Our results describe the potential role of low dose trastuzumab to increase sensitivity of oxaliplatin and cisplatin in HER2 amplified gastric cancer cells, which may be partially through downregulating the expression levels of telomere-related genes.

scholarly journals Investigating the Effects of Salvia chorassanica Bunge and Shoot Extracts on Gastric Cancer Cells: Evidence of Different Behavior on Various Tumor Grades

2020 ◽  
Vol 27 (3) ◽  
pp. 378-384
Author(s):  
Fatemeh Karami ◽  
Ahmad Dourandish Yazdi ◽  
Iman Salahshourifar ◽  
Mohsen Marvi Beigi
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Leaf Extract ◽  
P Value ◽  
Root Extract ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Expression Ratio ◽  
Anticancer Effects

Background: Different Salvia species have demonstrated anti-proliferative effects on various cancer cells. Owing to the poor literature on the anti-proliferative effects of Salvia species on gastric cancer cells, present study was conducted to determine the anticancer effects of a local Iranian Salvia, Salvia chorassanica, on two different gastric cell lines. Methods: Root, stem and leaf extract of Salvia chorassanica were prepared through maceration method and were then used to treat the AGS and MKN-45 cell lines in different concentrations. MTT assay was employed to determine the toxicity of all the types of extracts on the two studied cell lines. The expression of Bax, Bcl-2, Caspase3, MMP2 and MMP9 genes were determined through reverse transcription Real time PCR (RT-PCR). Results: Bunge and shoot extracts demonstrated toxicity in both cell lines which were more considerable in AGS cells treated with root extract. In contrary to AGS cells, Caspase3 gene was up-regulated in all types of treatment while the MMP2 and MMP9 genes were down-regulated (p-value<0.001). Except of the MKN-45 cells treated with leaf extract, Bax/Bcl-2 expression ratio was decreased in the treatment with all types of Salvia chorassanica extracts (p-value<0.001). Conclusion: Remarkable low IC50 concentration of root extract in MKN-45 cell line is indicating the significant cytotoxicity of Salvia chorassanica against gastric cancer cells. Moreover, gene expression analysis in MKN-45 needs further confirmation on the potential anti-metastatic roles of leaf and root extracts in higher grades of gastric cancer.

scholarly journals MiR-496 Inhibits the Proliferation Through Targeting LYN and AKT/mTOR Signaling Pathway in Gastric Cancer

2020 ◽  
Author(s):  
Rui Su ◽  
Enhong Zhao ◽  
Jun Zhang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
Human Gastric Cancer ◽  
Mtor Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Ags Cells

Abstract MiRNA operates as a tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis and metabolic process. In the present research, we investigated the effect and mechanism of miR496 in human gastric cancer cells. Cell proliferation was measured by CCK8 and clonogenic assay. Transwell test was performed to detect cell migration and invasion. Flow cytometry analysis was used to evaluate cell apoptosis. Bioinformatics software targetscan was used for the screening of miR-496’s target gene. MiR-496 was down regulated in three gastric cancer cell lines, SGC-790, AGS and MKN45 compared with normal gastric epithelial cell line GES-1. MiR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 h and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. In addition, miR-496 mimics induced the apoptosis through up regulating the levels of Bax and Active Caspase3 and down regulating the levels of Bcl-2 and Total Caspase3. Bioinformatics analysis showed that there was a binding site between miR-496 and LYN kinase (LYN). MiR-496 mimics could inhibit the expression of LYN in AGS cells. The overexpression of LYN blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496 in gastric cancer cells. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment of gastric cancer.

scholarly journals Chrysophanol Inhibits the Progression of Gastric Cancer by Activating NLRP3

2021 ◽  
Author(s):  
Hou Binfen ◽  
Li Zhao ◽  
Min Deng
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Antitumor Effects ◽  
Ags Cells ◽  
Anti Cancer ◽  
Colony Forming Assay

Abstract AimGastric cancer is one of the most common malignant tumors.Chrysophanol has been reported to have antitumor effects on a variety of cancers, but the role of chrysophanol in gastric cancer remains unclear. The aim of this study was to investigate the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of gastric cancer cells.MethodsMKN 28 and AGS cells were treatde with different concentrations of chrysophanol, then cell proliferation, migration,invasion and pyroptosis were decteed by CCK-8, Colony-forming assay, Wound Healing assay, Transwell and flow cytometry, respectively.Subsequently, NLRP3 siRNA was transfected into MKN 28 cells, cell proliferation pyroptosis, migration and invasion were reassessed in these transfected cells. The expression of caspase-1 and IL-1β in the downstream of NLRP3 was detected by qRT PCR and Western blot.ResultsChrysophanol significantly inhibited the proliferation of GC cells, promoted pyroptosis, inhibited cell migration and invasion, and up-regulated the expression level of NLRP3 inflammasome in GC cells. Silencing NLRP3 inhibited the effects of chrysophanol on proliferation, pyroptosis, migration and invasion of MKN 28 cells. Chrysophanol plays an anti-cancer role through high expression of NLRP3.CoclusionsChrysophanol can inhibit the proliferation, migration and invasion of gastric cancer cells by regulating NLRP3, promote the death of gastric cancer cells, and play an anti-tumor role,which is a clinical strategy with great potential for the treatment of gastric cancer.

scholarly journals Transcriptomic analysis reveals that bromodomain containing 9 controls signaling pathways in gastric cancer

2020 ◽  
Author(s):  
Yuan Wang ◽  
Chen Wang ◽  
Yu-Ting Mo ◽  
Wen Yi Tan ◽  
Xi-Yong Yu
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
The Cancer Genome Atlas ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
R Language ◽  
Gastric Cancers ◽  
Ppi Networks

Abstract Background According to the Cancer Genome Atlas, gastric cancers involve 30% BRD9 changes. Studying the signaling net controlled by BRD9 is important and provides useful information for the treatment of patients with gastric cancer and BRD9 alteration. Objective We performed this study to find the signaling pathways controlled by BRD9 in gastric cancer cells. Methods MGC-803 and AGS cells were selected as BRD9 overexpression and normal expression models, respectively, and added with BRD9 inhibitors BI9564 and BI7273, respectively. RNA-seq and limma R language were used to obtain differentially expressed genes (DEGs), and heatmap R language was employed for cluster analysis. Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to identify the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments, and STRING database was utilized to construct the protein–protein interaction (PPI) networks. Analysis was performed through Cytoscape software to determine the possible signaling pathway and target genes. Results Group MGC-803: 1204 and 1338 DEGs were found in MGC-803 cells added with BI9564 and BI7273, respectively, and 425 DEGs were found in the intersection of these two sets. AGS group: 974 and 1006 DEGs were found in AGS cells added with BI9564 and BI7273, respectively, and 382 DEGs were found in the intersection of these two sets. The DEG number in the intersection of groups MGC-803 and AGS was only 12, and only 3 of which showed the same regulation direction. Hence, these two types of gastric cancers are greatly altered in the signaling network. GO enrichment and KEGG signaling pathway analyses showed that in group MGC-803, BRD9 mainly controls cell adhesion molecule (CAM) pathway, and genes SPP1 and GNAO1 may play important an important role in the BRD9 controlling network. In group AGS, BRD9 mainly controls protein digestion and absorption pathway, and genes AR and GNGT2 have an important function in the BRD9 controlling network. Conclusion Comprehensive bioinformatics analyses were conducted to screen the DEGs and signaling pathways controlled by BRD9 in different gastric cancer cells. The findings provide a theoretical basis in curing patients with clinical gastric cancer.

DNA methyltransferase 3 beta regulates ras related domain family 1 methylation leading to enhanced proliferation and migration in gastric cancer cells

2020 ◽  
Vol 10 (10) ◽  
pp. 1628-1637
Author(s):  
Haiwen Li ◽  
Jingwei Li ◽  
Jinquan Li ◽  
Jiaying Zhong ◽  
Yiming Xie ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Dna Hypermethylation ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dna Methyltransferase Inhibitors ◽  
And Migration ◽  
Proliferation And Migration

Silencing expression of RASSF1A, which is induced by DNA hypermethylation, contributes to proliferation and migration in gastric cancer. However, the molecular mechanisms of this process remain unclear. In order to investigate the effect and mechanisms of RASSF1A methylation on proliferation and migration of gastric cancer, DNA methyltransferase inhibitors (5-AZA-CdR) were used to interfere with expression of DNMT3B and RASSF1A in gastric cancer AGS cells. Fe3O4–SiO2 nanoparticles were used to extract mRNA for RT-qPCR, and RT-qPCR and western blotting were used to measure the effect of RASSF1A expression on the expression of Caspase 3, Bcl-2, and Bax in AGS cells. MTT and cell scratch assays were used to assess the proliferation and migration of AGS cells. Our findings show that DNA methyltransferase inhibitors inhibit expression of DNMT3B, which leads to an increase in the expression of RASSF1A, Caspase3, and Bax at both the mRNA and protein levels, and inhibits the expression of Bcl-2. Thus, inhibiting the expression of DNMT3B and altering levels of DNA methylation can promote the expression of RASSF1A, regulate the expression of apoptosis-related genes, and inhibit proliferation and migration of gastric cancer cells. It is helpful to explore the pathological mechanism of endometrial cancer and provide theoretical basis for RASSF1A as a potential therapeutic target of gastric cancer.

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