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

  • Authors:
    • Zhi Gang 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
  • View Affiliations

  • Published online on: April 1, 2010     https://doi.org/10.3892/or_00000747
  • Pages: 1167-1172
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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.

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April 2010
Volume 23 Issue 4

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

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Spandidos Publications style
Wang ZG, Fukazawa T, Nishikawa T, Watanabe N, Sakurama K, Motoki T, Hatakeyama S, Omori O, Ohara T, Tanabe S, Tanabe S, et al: RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer. Oncol Rep 23: 1167-1172, 2010
APA
Wang, Z.G., Fukazawa, T., Nishikawa, T., Watanabe, N., Sakurama, K., Motoki, T. ... Naomoto, Y. (2010). RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer. Oncology Reports, 23, 1167-1172. https://doi.org/10.3892/or_00000747
MLA
Wang, Z. G., 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."RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer". Oncology Reports 23.4 (2010): 1167-1172.
Chicago
Wang, Z. G., 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."RAD001 offers a therapeutic intervention through inhibition of mTOR as a potential strategy for esophageal cancer". Oncology Reports 23, no. 4 (2010): 1167-1172. https://doi.org/10.3892/or_00000747