TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells

  • Authors:
    • Zhi Gang Wang
    • Takuya Fukazawa
    • Toshio Nishikawa
    • Nobuyuki Watanabe
    • Kazufumi Sakurama
    • Takayuki Motoki
    • Munenori Takaoka
    • Shinji Hatakeyama
    • Osamu Omori
    • Toshiaki Ohara
    • Shunsuke Tanabe
    • Yasuhiro Fujiwara
    • Yasuhiro Shirakawa
    • Tomoki Yamatsuji
    • Noriaki Tanaka
    • Yoshio Naomoto
  • View Affiliations

  • Published online on: December 1, 2008     https://doi.org/10.3892/or_00000168
  • Pages: 1473-1477
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

Related Articles

Journal Cover

December 2008
Volume 20 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Wang ZG, Fukazawa T, Nishikawa T, Watanabe N, Sakurama K, Motoki T, Takaoka M, Hatakeyama S, Omori O, Ohara T, Ohara T, et al: TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncol Rep 20: 1473-1477, 2008
APA
Wang, Z.G., Fukazawa, T., Nishikawa, T., Watanabe, N., Sakurama, K., Motoki, T. ... Naomoto, Y. (2008). TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells. Oncology Reports, 20, 1473-1477. https://doi.org/10.3892/or_00000168
MLA
Wang, Z. G., 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, Y."TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells". Oncology Reports 20.6 (2008): 1473-1477.
Chicago
Wang, Z. G., 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, Y."TAE226, a dual inhibitor for FAK and IGF-IR, has inhibitory effects on mTOR signaling in esophageal cancer cells". Oncology Reports 20, no. 6 (2008): 1473-1477. https://doi.org/10.3892/or_00000168