RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 μM 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.

Original languageEnglish
Pages (from-to)1167-1172
Number of pages6
JournalOncology reports
Volume23
Issue number4
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Cell growth
  • Esophageal cancer cells
  • RAD001 (everolimus)
  • mTOR signaling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer'. Together they form a unique fingerprint.

  • Cite this

    Wang, G. Z., Fukazawa, T., Nishikawa, T., Watanabe, N., Sakurama, K., Motoki, T., Hatakeyama, S., Omori, O., Ohara, T., Tanabe, S., Fujiwara, Y., Takaoka, M., Shirakawa, Y., Yamatsuji, T., Tanaka, N., & Naomoto, Y. (2010). RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer. Oncology reports, 23(4), 1167-1172. https://doi.org/10.3892/or-00000747