2-Deoxy-d-glucose enhances TRAIL-induced apoptosis in human gastric cancer cells through downregulating JNK-mediated cytoprotective autophagy

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.

Download Full-text

Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells

PLoS ONE ◽

10.1371/journal.pone.0149120 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0149120 ◽

Cited By ~ 18

Author(s):

Yanfei Jia ◽

Haiji Sun ◽

Hongqiao Wu ◽

Huilin Zhang ◽

Xiuping Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Akt Signaling ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Induced Apoptosis

Download Full-text

Effect of exogenous FHIT gene expression on vincristine-induced apoptosis of human gastric cancer cells MKN-28

World Chinese Journal of Digestology ◽

10.11569/wcjd.v16.i30.3367 ◽

2008 ◽

Vol 16 (30) ◽

pp. 3367

Author(s):

Jun Wang ◽

Xiao-Ming Duan ◽

Zi-Hua Zhou ◽

Xiu-Sheng He

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Gastric Cancer Cells ◽

Fhit Gene ◽

Induced Apoptosis

Download Full-text

miR193b Promotes Apoptosis of Gastric Cancer Cells via Directly Mediating the Akt Pathway

BioMed Research International ◽

10.1155/2020/2863236 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Ruyue Tian ◽

Hailun Jiang ◽

Linlin Shao ◽

Yang Yu ◽

Qingdong Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Critical Role ◽

Pik3ca Mutation ◽

Akt Pathway ◽

Human Gastric Cancer ◽

Tumor Type ◽

Gastric Cancer Cells ◽

Induced Apoptosis

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues (p<0.05) and human gastric cancer cell lines (p<0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage (p<0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis (p<0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways (p<0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.

Download Full-text