Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer

BMC Cancer

Research Article

Xin-juan Fang¹  Ying Tian²  Ying-bo Chen³  You-qing Zhan³  Zhi-wei Zhou³  Da-zhi Xu³  Xiao-wei Sun³  Yuan-fang Li³  Yuan-xiang Guan³  Wei Li³  Tong-yu Lin⁴  Qi-rong Geng⁴  Mu-yan Cai⁵ 

[1] Department of Pathology, the Sixth Affiliated Hospital, Sun Yat-sen University, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, 510060, Guangzhou, China;Department of Gastric & pancreatic Surgery, Cancer Center, Sun Yat-sen University, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, 510060, Guangzhou, China;Department of Medical Oncology, Cancer Center, Sun Yat-sen University, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, 510060, Guangzhou, China;Department of Pathology, Cancer Center, Sun Yat-sen University, 510060, Guangzhou, China;

关键词: Gastric Cancer;    Overall Survival;    Rapamycin;    Gastric Cancer Cell;    Gastric Cancer Patient;   

DOI  :  10.1186/1471-2407-10-536

 received in 2009-09-20, accepted in 2010-10-07,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer.MethodsThe expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines.ResultsImmunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.ConclusionsIn gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.

【 授权许可】

Unknown   
© Xu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.