TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells.
TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells.
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DOI：
10.3892/or_00000168
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发表时间：
2008
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;M. Takaoka;S. Hatakeyama;O. Omori;T. Ohara;S. Tanabe;Y. Fujiwara;Y. Shirakawa;T. Yamatsuji;N. Tanaka;Y. Naomoto
中科院分区：
文献类型：
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作者：
Zhi Gang Wang;T. Fukazawa;T. Nishikawa;Nobuyuki Watanabe;Kazufumi Sakurama;Takayuki Motoki;M. Takaoka;S. Hatakeyama;O. Omori;T. Ohara;S. Tanabe;Y. Fujiwara;Y. Shirakawa;T. Yamatsuji;N. Tanaka;Y. Naomoto
食管癌是世界上最具侵袭性的癌症之一。新的预防和治疗策略倾向于针对细胞生长信号转导途径中涉及的关键分子。众所周知，FAK 和 mTOR 是细胞生长的重要控制器。 TAE226 是一种新型小分子化合物，是 FAK 和 IGF-IR 的有效 ATP 竞争性抑制剂。 TAE226 可以阻断 FAK 和 IGF-IR 信号通路。本研究的目的是探讨TAE226对mTOR信号传导的抑制作用以及抑制细胞生长的机制。我们检测了食管癌细胞（SEG-1）和正常食管上皮细胞（KOB-13）中mTOR和S6的表达以及TAE226对SEG-1细胞的功效。与KOB-13细胞相比，SEG-1细胞中mTOR和S6过表达。 TAE226 抑制 mTOR、Akt、p70S6K 和 S6 的表达以及 mTOR (Ser2448)、Akt (Ser473)、p70S6K (Thr389) 和 S6 (Ser240/244) 的磷酸化。结果，TAE226 引起细胞生长（数量）和细胞形状损伤的剂量依赖性下降。总之，这些数据表明TAE226对mTOR信号传导和食管癌细胞生长具有有效的抑制作用，表明TAE226在食管癌治疗中具有潜在的应用。
Esophageal cancer is one of the most aggressive cancers in the world. Novel preventive and therapeutic strategies tend to target the key molecules involved in the signaling transduction pathways for cell growth. It is known that FAK and mTOR are important controllers of cell growth. TAE226, a novel small molecule compound, is a potent ATP competitive inhibitor of FAK and IGF-IR. TAE226 can block FAK and IGF-IR signaling pathways. The purpose of this study was to explore the inhibitory effects on mTOR signaling and the mechanism of cell growth suppression by TAE226. We examined the expression of mTOR and S6 in esophageal cancer cells (SEG-1) and normal esophageal epithelial cells (KOB-13) and the efficacy of TAE226 against SEG-1 cells. mTOR and S6 were overexpressed in SEG-1 cells compared with KOB-13 cells. TAE226 inhibited the expression of mTOR, Akt, p70S6K and S6 as well as the phosphorylation of mTOR (Ser2448), Akt (Ser473), p70S6K (Thr389) and S6 (Ser240/244). As a result, TAE226 induced a dose-dependent decrease in cell growth (number) and damage in the cell shape. Together, these data show that TAE226 has potent inhibitory effects on mTOR signaling and esophageal cancer cell growth indicating that TAE226 has potential application in esophageal cancer treatment.