Gastric cancer is the fourth most common type of cancer. Liver–intestine cadherin (CDH17) has been found to be involved in the proliferation and apoptosis of gastric cancer cells. Cisplatin is one of the most widely used antineoplastic agents in the treatment of solid tumor and hematological malignancies. However, the mechanism of enhancing cisplatin-inducing effects on human gastric cancer BGC823 cells by blocking CDH17 gene, both in vitro and in vivo, remains to be clarified. In this study, we investigated the signaling pathway by which cisplatin induces apoptosis by blocking CDH17 gene in gastric cancer BGC823 cells. Our results indicate that down-expression of CDH17 gene can enhance apoptosis-inducing effects of cisplatin on human gastric cancer BGC823 cells. The expression levels of Bax and Cyt-c proteins were upregulated, but the expression levels of Bcl-2 and Bcl-xL proteins were downregulated by blocking CDH17 gene in gastric cancer BGC823 cells after treatment with cisplatin. Moreover, down-expression of CDH17 enhanced the efficacy of cisplatin-induced inhibition of tumor growth in nude mice via apoptosis induction. Down-expression of CDH17 gene can significantly improve apoptosis-inducing effects of cisplatin in vitro and in vivo, which is a new strategy to improve chemotherapeutic effects on gastric cancer.
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This work was supported by Wuhan Science and Technology Bureau of applied basic research projects (2015060101010064), Hubei Province Natural Science Foundation of China (2013CFB358), and Project of Health and Family Planning Commission of Wuhan Municipality (WX15C09 and WX14C18). We sincerely thank Dr. Wei Guo Dong and Mr. Hong Xia from the Institute of Gastroenterology and Hepatology, Renmin Hospital of Wuhan University.
Conflict of interest
The authors declare that they have no competing interests.
Meng Liu and Zheng Han contributed equally to this work.