scholarly journals Reversal of Multidrug Resistance by the Chinese Medicine Yiqi Jianpi Huaji Decoction and the Mechanism of Action in Human Gastric Cancer SGC7901/VCR Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Bing Li ◽  
Yang Li ◽  
Chen Yu ◽  
Yong-Ming He
Keyword(s):  
Gastric Cancer ◽  
Mechanism Of Action ◽  
Low Dose ◽  
Chemotherapeutic Agents ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Future Studies ◽  
Increased Sensitivity ◽  
Induced Apoptosis

Yiqi Jianpi Huaji Decoction (YJHD), a traditional Chinese medicinal formula composed of twelve ingredients, has recently been reported to have a good clinical curative effect. The purpose of the present study was to evaluate the effects of YJHD on SGC7901/VCR gastric cancer cells and to elucidate the possible mechanism of action. First, the effects of a low dose of YJHD in combination with chemotherapeutic agents on SGC7901/VCR cells were assessed using the CCK-8 assay and flow cytometry, and the effects of YJHD on genes and proteins involved in drug resistance (MDR1, MRP, TUBB3, STMN1, and TS) were evaluated. Furthermore, transfection of SGC7901/VCR cells with siRNAs targeting these genes inhibited their expression, and the efficacy of vincristine against the cells was dramatically improved in vitro when these genes were silenced. These results demonstrate that low-dose YJHD inhibited cell proliferation, induced apoptosis, reversed MDR, and increased sensitivity to chemotherapeutic agents in vitro by downregulating P-gp, MRP, TUBB3, and STMN1 expression. MDR can be reversed by siRNAs targeting genes involved in MDR, and this strategy for cancer treatment should be evaluated in future studies.

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 The Herb Medicine Formula “Chong Lou Fu Fang” Increases the Cytotoxicity of Chemotherapeutic Agents and Down-Regulates the Expression of Chemotherapeutic Agent Resistance-Related Genes in Human Gastric Cancer CellsIn Vitro

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Yongping Liu ◽  
Yang Ling ◽  
Wenjing Hu ◽  
Li Xie ◽  
Lixia Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Chemotherapeutic Agent ◽  
Chemotherapeutic Agents ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Herb Medicine

The herb medicine formula “Chong Lou Fu Fang” (CLFF) has efficacy in inhibiting the proliferation of human gastric cancerin vitroandin vivo. To explore the potentially useful combination of CLFF with chemotherapeutic agents commonly used in gastric cancer therapy, we assess the interaction between CLFF and these chemotherapeutic agents in both SGC-7901 cell lines and BGC-823 cell lines using a median effect analysis and apoptosis analysis, and we also investigate the influence of CLFF on chemotherapeutic agent-associated gene expression. The synergistic analysis indicated that CLFF had a synergistic effect on the cytotoxicity of 5-fluorouracil (5-FU) in a relative broad dose inhibition range (20–95% fraction affected in SGC-7901cell lines and 5–65% fraction affected in BGC-823 cell lines), while the synergistic interaction between CLFF and oxaliplatin or docetaxel only existed in a low dose inhibition range (≤50% fraction affected in both cell lines). Combination of CLFF and chemotherapeutic agents could also induce apoptosis in a synergistic manner. After 24 h, CLFF alone or CLFF combination with chemotherapeutic agents could significantly suppress the levels of expression of chemotherapeutic agent resistance related genes in gastric cancer cells. Our findings indicate that there are useful synergistic interactions between CLFF and chemotherapeutic agents in gastric cancer cells, and the possible mechanisms might be partially due to the down-regulation of chemotherapeutic agent resistance related genes and the synergistic apoptotic effect.

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 Cre-loxP-mediated bax gene activation reduces growth rate and increases sensitivity to chemotherapeutic agents in human gastric cancer cells

2000 ◽  
Vol 7 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Koga Komatsu ◽  
Susumu Suzuki ◽  
Tooru Shimosegawa ◽  
Jun-ichi Miyazaki ◽  
Takayoshi Toyota
Keyword(s):  
Gastric Cancer ◽  
Growth Rate ◽  
Cancer Cells ◽  
Gene Activation ◽  
Chemotherapeutic Agents ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Bax Gene

Oleanolic acid induces autophagic death in human gastric cancer cells in vitro and in vivo

2016 ◽  
Vol 40 (7) ◽  
pp. 770-778 ◽  
Author(s):  
Hao Nie ◽  
Yu Wang ◽  
Yong Qin ◽  
Xing-Guo Gong
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Oleanolic Acid ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells

scholarly journals Potent and specific MTH1 inhibitors targeting gastric cancer

2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Wenjuan Zhou ◽  
Liying Ma ◽  
Jing Yang ◽  
Hui Qiao ◽  
Lingyu Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Malignant Tumors ◽  
Inhibitory Effect ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Dntp Pool ◽  
Cancer Tissues

Abstract Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells. Using an in vitro MTH1 inhibitor screening system, the compounds available in our laboratory were screened and the small molecules containing 5-cyano-6-phenylpyrimidine structure were firstly found to show potently and specifically inhibitory effect on MTH1, especially compound MI-743 with IC50 = 91.44 ± 1.45 nM. Both molecular docking and target engagement experiments proved that MI-743 can directly bind to MTH1. Moreover, MI-743 could not only inhibit cell proliferation in up to 16 cancer cell lines, especially gastric cancer cells HGC-27 and MGC-803, but also significantly induce MTH1-related 8-oxo-dG accumulation and DNA damage. Furthermore, the growth of xenograft tumours derived by injection of MGC-803 cells in nude mice was also significantly inhibited by MI-743 treatment. Importantly, MTH1 knockdown by siRNA in those two gastric cancer cells exhibited the similar findings. Our findings indicate that MTH1 is highly expressed in human gastric cancer tissues and cell lines. Small molecule MI-743 with 5-cyano-6-phenylpyrimidine structure may serve as a novel lead compound targeting the overexpressed MTH1 for gastric cancer treatment.

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