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人 EAG 相关基因表达对顺铂诱导人胃癌细胞凋亡是必需的。

Human ether-à-go-go-related gene expression is essential for cisplatin to induce apoptosis in human gastric cancer.

机构信息

Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.

出版信息

Oncol Rep. 2012 Feb;27(2):433-40. doi: 10.3892/or.2011.1515. Epub 2011 Oct 21.

Abstract

Human ether-à-go-go-related gene (HERG) is over-expressed in a wide range of human cancers and regulates survival, migration, and apoptosis. The aim of this study was to investigate the role of HERG in cisplatin-induced apoptosis in gastric cancer in vitro and in vivo. siRNA was used to silence HERG expression. HERG expression was detected by Western blot analysis in vitro, and further confirmed by immunohistochemistry in vivo. Chemosensitivity to cisplatin in gastric cancer cells was analyzed with a Cell Counting Kit-8 assay. Apoptosis was detected by flow cytometry in vitro, and in situ apoptotic SGC7901 human gastric tumor cells in BALB/c nude mice were detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Our results show that cisplatin increased the expression of HERG in gastric cancer cells. Silencing HERG inhibited the apoptosis induced by cisplatin both in vitro and in vivo, by attenuating the cisplatin effects on Bcl-2, Bax and active caspase-3. The role of HERG in modulation of cisplatin-induced apoptosis suggests that HERG may provide a new potential target for cisplatin chemotherapy in human gastric cancer.

摘要

人类 ether-à-go-go 相关基因(HERG)在广泛的人类癌症中过度表达,调节存活、迁移和细胞凋亡。本研究旨在探讨 HERG 在体外和体内顺铂诱导胃癌细胞凋亡中的作用。使用 siRNA 沉默 HERG 表达。体外通过 Western blot 分析检测 HERG 表达,并通过体内免疫组化进一步证实。用细胞计数试剂盒-8 分析检测胃癌细胞对顺铂的化疗敏感性。体外通过流式细胞术检测凋亡,并用末端脱氧核苷酸转移酶 dUTP 缺口末端标记法检测 BALB/c 裸鼠原位凋亡 SGC7901 人胃癌肿瘤细胞。我们的结果表明,顺铂增加了胃癌细胞中 HERG 的表达。沉默 HERG 抑制了体外和体内顺铂诱导的凋亡,减弱了顺铂对 Bcl-2、Bax 和活性 caspase-3 的作用。HERG 在调节顺铂诱导的凋亡中的作用表明,HERG 可能为人类胃癌的顺铂化疗提供新的潜在靶点。

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