RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer.
RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer.
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DOI：
10.3892/or_00000747
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发表时间：
2010-04
期刊：
影响因子：
4.2
通讯作者：
Zhi Gang Wang;T. Fukazawa;T. Nishikawa;Nobuyuki Watanabe;Kazufumi Sakurama;Takayuki Motoki;S. Hatakeyama;O. Omori;T. Ohara;S. Tanabe;Y. Fujiwara;M. Takaoka;Y. Shirakawa;T. Yamatsuji;N. Tanaka;Y. Naomoto
中科院分区：
文献类型：
--
作者：
Zhi Gang Wang;T. Fukazawa;T. Nishikawa;Nobuyuki Watanabe;Kazufumi Sakurama;Takayuki Motoki;S. Hatakeyama;O. Omori;T. Ohara;S. Tanabe;Y. Fujiwara;M. Takaoka;Y. Shirakawa;T. Yamatsuji;N. Tanaka;Y. Naomoto
食管癌是世界上最常见的癌症之一。肿瘤的靶向治疗策略正在发展，并显示出良好的抗肿瘤效果。已知mTOR是细胞生长的重要控制器。RAD 001（依维莫司）是mTOR的特异性抑制剂，可以阻断mTOR信号通路。本研究旨在探讨RAD 001对mTOR信号的抑制作用及其抑制细胞生长的机制。我们检测了SEG-1食管癌细胞和KOB-13正常食管上皮细胞中mTOR、p70 S6 K和S6的表达以及RAD 001对SEG-1食管癌细胞的疗效。与KOB-13正常食管上皮细胞相比，SEG-1食管癌细胞中mTOR、p70 S6 K和S6均过表达。SEG-1食管癌细胞对RAD 001敏感。RAD 001浓度大于0.33 μ M时，细胞存活率与对照组相比有显著性差异（P<0.01）。RAD 001可不同程度地抑制mTOR（Ser 2448）和S6（Ser 240/244）的磷酸化以及mTOR、p70 S6 K和S6的表达。结果，RAD 001诱导细胞增殖、G1/S期阻滞和细胞形状损伤的剂量依赖性降低。综上所述，这些数据表明，RAD 001可以在体外抑制SEG-1食管癌细胞中的mTOR信号传导和增殖。它通过抑制mTOR作为食管癌的潜在策略提供了治疗干预。
Esophageal cancer is one of the most frequently occurring cancers in the world. Targeting therapy strategy of cancer with specific inhibitors is developing and has showed promising antitumor efficacy. It is known that mTOR is an important controller of cell growth. RAD001 (everolimus) is a specific inhibitor of mTOR that can block the mTOR signaling pathway. The purposes of this study was to explore the inhibitory effects of RAD001 on mTOR signaling and the mechanism of cell growth suppression by RAD001. We examined both the expression of mTOR, p70S6K and S6 in SEG-1 esophageal cancer cells and KOB-13 normal esophageal epithelial cells and the efficacy of RAD001 against SEG-1 esophageal cancer cells. mTOR, p70S6K and S6 were overexpressed in SEG-1 esophageal cancer cells compared with KOB-13 normal esophageal epithelial cells. SEG-1 esophageal cancer cells were sensitive to RAD001. The survival rate of the cells treated with RAD001 over 0.33 microM was significantly different compared with that of control (P<0.01). RAD001 inhibited the phosphorylation of mTOR (Ser2448) and S6 (Ser240/244) in different grades and the expressions of mTOR, p70S6K and S6. As a result, RAD001 induced a dose-dependent decrease in cell proliferation, G1/S arrest and damage of cell shape. Taken together, these data showed that RAD001 can inhibit mTOR signaling and proliferation in SEG-1 esophageal cancer cells in vitro. It offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer.