Abstract:
: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.
journal_name
Oncol Repjournal_title
Oncology reportsauthors
Wang ZG,Fukazawa T,Nishikawa T,Watanabe N,Sakurama K,Motoki T,Takaoka M,Hatakeyama S,Omori O,Ohara T,Tanabe S,Fujiwara Y,Shirakawa Y,Yamatsuji T,Tanaka N,Naomoto Ysubject
Has Abstractpub_date
2008-12-01 00:00:00pages
1473-7issue
6eissn
1021-335Xissn
1791-2431journal_volume
20pub_type
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