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

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.

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

Current Molecular Medicine ◽

10.2174/1566524020666201120113538 ◽

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.

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Berberine Improves Chemo-Sensitivity to Cisplatin by Enhancing Cell Apoptosis and Repressing PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer

Frontiers in Pharmacology ◽

10.3389/fphar.2020.616251 ◽

2020 ◽

Vol 11 ◽

Author(s):

Yingying Kou ◽

Bending Tong ◽

Weiqing Wu ◽

Xiangqing Liao ◽

Min Zhao

Keyword(s):

Gastric Cancer ◽

Drug Resistance ◽

Multidrug Resistance ◽

Cell Viability ◽

Cancer Cells ◽

Cell Apoptosis ◽

Mtor Signaling ◽

Multi Drug Resistance ◽

Gastric Cancer Cells

Gastric cancer is one of the most common malignancies ranks as the second leading cause of cancer-related mortality in the world. Cisplatin (DDP) is commonly used for gastric cancer treatment, whereas recurrence and metastasis are common because of intrinsic and acquired DDP-resistance. The aim of this study is to examine the effects of berberine on the DDP-resistance in gastric cancer and explore the underling mechanisms. In this study, we established the DDP-resistant gastric cancer cells, where the IC50 values of DDP in the BGC-823/DDP and SGC-7901/DDP were significantly higher than that in the corresponding parental cells. Berberine could concentration-dependently inhibited the cell viability of BGC-823 and SGC-7901 cells; while the inhibitory effects of berberine on the cell viability were largely attenuated in the DDP-resistant cells. Berberine pre-treatment significantly sensitized BGC-823/DDP and SGC-7901/DDP cells to DDP. Furthermore, berberine treatment concentration-dependently down-regulated the multidrug resistance-associated protein 1 and multi-drug resistance-1 protein levels in the BGC-823/DDP and SGC7901/DDP cells. Interestingly, the cell apoptosis of BGC-823/DDP and SGC-7901/DDP cells was significantly enhanced by co-treatment with berberine and DDP. The results from animals also showed that berberine treatment sensitized SGC-7901/DDP cells to DDP in vivo. Mechanistically, berberine significantly suppressed the PI3K/AKT/mTOR in the BGC-823/DDP and SGC-7901/DDP cells treated with DDP. In conclusion, we observed that berberine sensitizes gastric cancer cells to DDP. Further mechanistic findings suggested that berberine-mediated DDP-sensitivity may be associated with reduced expression of drug transporters (multi-drug resistance-1 and multidrug resistance-associated protein 1), enhanced apoptosis and repressed PI3K/AKT/mTOR signaling.

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

Nucleic Acids Research ◽

10.1093/nar/gkt1275 ◽

2013 ◽

Vol 42 (5) ◽

pp. 2988-2998 ◽

Cited By ~ 48

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.

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

European Journal of Inflammation ◽

10.1177/2058739219845534 ◽

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.

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Compare the Effects of Magnolol on Gastric Cancer Cells Through c-Jun N-Terminal Kinase Signaling Pathway and Gold Magnetic

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18688 ◽

2021 ◽

Vol 21 (2) ◽

pp. 943-948

Author(s):

Yu Chen ◽

Xiuyun He ◽

Dagang Feng ◽

Shijie Li

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Viability ◽

Cancer Cells ◽

Control Group ◽

Magnetic Nanocomposites ◽

Magnetic Composite ◽

Composite Nanomaterials ◽

Gastric Cancer Cells ◽

Cell Proliferation Inhibition

This article explores the effects and mechanisms of magnolol on the proliferation of gastric cancer cells as well as the apoptosis. First, 0 (control group), 20, 40, and 80 /x mol/L magnolol were observed on SGC-7901 cells for 24, 48, and 72 h. We use MTT method to measure the cell viability, and apoptosis and cells were detected by flow cytometry. Cell proliferation inhibition rate, apoptosis and cell cycle experiments showed that P-value < 0.05 means the difference is statistically significant. And the results which compare the control group, the 20, 40, and 80 /x mol/L show that honokiol had lower cell viability (P < 0.01), increased apoptotic rate (P < 0.01), and cell cycle stay in the G1 phase (P < 0.01), so we found that honokiol may suppress the proliferation of SGC-7901 cells and stimulate apoptosis by regulating cyclin and apoptosis-related proteins. With the development of nanomaterials synthesis technology and application in biomedicine, gold magnetic composite nanomaterials have unique properties, so they have been widely concerned in many applications. We combine gold and magnetic nanomaterials through other nanostructures to achieve the integration of diagnosis and treatment of tumors. We have synthesized two kinds of gold magnetic nanocomposites, GNR-PPy-FA nanocomposites. With the role of chemotherapy and heat and light therapy, GNR-PPy-FA nanocomposites have high light-to-heat conversion efficiency. Cell experiments verify the effect of chemotherapy and photothermal treatment of composite nanomaterials. After incubation with gold magnetic composite nanomaterials, the cell survival rate of tumor cells decreased to about 15%. In addition, both types of gold magnetic nanocomposites have the ability to dually target cancer cells, and the modification of folic acid and cancer cell membranes makes the material more biocompatible.

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Periplocin Extracted from Cortex Periplocae Induced Apoptosis of Gastric Cancer Cells via the ERK1/2-EGR1 Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000445555 ◽

2016 ◽

Vol 38 (5) ◽

pp. 1939-1951 ◽

Cited By ~ 20

Author(s):

Lei Li ◽

Lian-Mei Zhao ◽

Su-li Dai ◽

Wen-Xuan Cui ◽

Hui-Lai Lv ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Viability ◽

Cancer Cells ◽

Inhibitory Effect ◽

Tunel Staining ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Induced Apoptosis

Background/Aims: Periplocin is extracted from the traditional herbal medicine cortex periplocae, which has been reported to suppress the growth of cancer cells. However, little is known about its effect on gastric cancer cells. Methods: Gastric cancer cells were treated with periplocin, and cell viability was assessed using MTS assay. Flow cytometry and TUNEL staining were performed to evaluate apoptosis, and protein expression was examined by western blotting. Microarray analysis was used to screen for changes in related genes. Results: We found that periplocin had an inhibitory effect on gastric cancer cell viability in a dose-dependent manner. Periplocin inhibited cell viability via the ERK1/2-EGR1 pathway to induce apoptosis. Periplocin also inhibited the growth of tumor xenografts and induced apoptosis in vivo. Conclusion: Our results show that periplocin inhibits the proliferation of gastric cancer cells and induces apoptosis in vitro and in vivo, indicating its potential to be used as an antitumor drug.

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

Pharmaceutical Sciences ◽

10.34172/ps.2020.99 ◽

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.

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

10.21203/rs.3.rs-61573/v1 ◽

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.

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Chrysophanol Inhibits the Progression of Gastric Cancer by Activating NLRP3

10.21203/rs.3.rs-1073406/v1 ◽

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.

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