Department of Gastroenterology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, 430060, China.
Cancer Gene Ther. 2018 Feb;25(1-2):1-9. doi: 10.1038/s41417-017-0001-2. Epub 2017 Dec 4.
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.
胃癌是第四大常见癌症类型。肝肠钙黏蛋白(CDH17)已被发现参与胃癌细胞的增殖和凋亡。顺铂是治疗实体瘤和血液恶性肿瘤中最广泛使用的抗肿瘤药物之一。然而,通过阻断 CDH17 基因在体外和体内增强顺铂对人胃癌 BGC823 细胞诱导作用的机制仍需阐明。在这项研究中,我们研究了通过阻断胃癌 BGC823 细胞中的 CDH17 基因,顺铂诱导细胞凋亡的信号通路。我们的结果表明,下调 CDH17 基因可以增强顺铂对人胃癌 BGC823 细胞的凋亡诱导作用。阻断 CDH17 基因后,顺铂处理的胃癌 BGC823 细胞中 Bax 和 Cyt-c 蛋白的表达水平上调,而 Bcl-2 和 Bcl-xL 蛋白的表达水平下调。此外,下调 CDH17 基因通过诱导细胞凋亡增强了顺铂抑制裸鼠肿瘤生长的疗效。下调 CDH17 基因可显著提高顺铂在体外和体内的凋亡诱导作用,这是提高胃癌化疗效果的新策略。