Blockade of TRPC6 channels induced G2/M phase arrest and suppressed growth in human gastric cancer cells

被引：99

作者：

Cai, Rong ^{[2
]}

Ding, Xia ^{[1
,3
]}

Zhou, Kechun ^{[1
,3
]}

Shi, Yu ^{[4
,5
]}

Ge, Ruiliang ^{[6
]}

Ren, Gang ^{[7
]}

Jin, Yening ^{[2
]}

Wang, Yizheng ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Neurosci, SIBS, Lab Neural Signal Transduct, Shanghai 200031, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Dept Radiochemotherapy, Ruijin Hosp, Shanghai, Peoples R China

[3] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China

[4] Fudan Univ, ZhongShan Hosp, Shanghai, Peoples R China

[5] Fudan Univ, Shanghai Med Sch, Shanghai, Peoples R China

[6] Second Mil Med Univ, Eastern Hepatobiliary Hosp, Shanghai, Peoples R China

[7] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai, Peoples R China

来源：

INTERNATIONAL JOURNAL OF CANCER | 2009年 / 125卷 / 10期

基金：

中国国家自然科学基金;

关键词：

TRPC6; gastric cancer; cell cycle; RECEPTOR POTENTIAL CHANNELS; PROLIFERATION; CA2+; CHECKPOINTS; ACTIVATION; EXPRESSION; ENTRY;

D O I：

10.1002/ijc.24551

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Channels formed by file canonical transient receptor potential (TRPC) subfamily of proteins are Ca2+-permeable, nonselective cation channels with various functions. Through I phospholipase C (PLO-dependent mechanism TRPC6, a member of TRPC subfamily. can be activated by receptor tyrosine kinases (RTK) or G protein-coupled receptors (GPCR),. which are implicated in cell proliferation and human malignancies. Here, we report that TRPC6 has a critical role in human gastric cancer development. Expression of TRPC6 Was greatly upregulated in human gastric cancer epithelial cells compared with that in normal gastric epithelial cells. Treatment of AGS or MKN45 cells, human gastric cancer cell lines, with SKF96365, an agent known to inhibit TRPC channels. arrested cell cycle in G2/M phase and suppressed cell growth. Importantly, expressing a dominant negative mutant of TRPC6 (DNC6) in these cells also arrested cell cycle in G2/M phase all inhibited cell growth. The Ca2+ elevation in the MKN45 cells evoked by histamine war, inhibited by SKF96365 and DNC6. Moreover, inhibition of TRPC6 suppressed the formation of gastric tumors in nude mice. These results suggest that Ca2+ elevation regulated by TRPC6 channels is essential for G2/M phase transition and for the development of gastric cancers. (C) 2009 UICC

引用

页码：2281 / 2287

页数：7

共 20 条

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