The novel mTOR inhibitor CCI-779 (temsirolimus) induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cells

Cancer Cell International

Zhigang Wang¹  Yuhao Chen¹  Haixia Fu¹  Xiaojing Wang¹  Manlin Wu¹  Yan Liang¹  Shuyu Li¹ 

[1] College of Life Science, Inner Mongolia University, 010021, Hohhot, P.R. China

关键词: Liver cancer cell;    Cell growth;    mTOR signaling;    CCI-779 (temsirolimus);   

Others  :  794092
DOI  :  10.1186/1475-2867-13-30

 received in 2013-01-28, accepted in 2013-03-20,  发布年份 2013

【 摘 要 】

Background

Liver cancer is one of the most frequent cancers in the world. Targeted therapy of cancer with specific inhibitors is developing and has shown promising antitumor efficacy. CCI-779 (temsirolimus), a specific inhibitor of mTOR (mammalian target of rapamycin), can block the mTOR signaling pathway. Here, we systematically examined the expression of mTOR and its downstream targets in liver cancer cells and normal liver cells, then investigated inhibitory effects of CCI-779 on mTOR signaling pathway and its role in regulating liver cancer cell growth.

Methods

The expression of mTOR and its downstream targets in Bel-7402 liver cancer cells and HL-7702 normal liver cells were examined by western blot. The mTOR specific inhibitor (CCI-779) was used to treat Bel-7402 cells to identify its effects on Bel-7402 cell growth and activity of mTOR signaling pathway in vitro. Cell viability tests were performed after the treatment of CCI-779. Western blot was applied to assess the changes of mTOR pathway and flow cytometry was used to analyze cell cycle of Bel-7402 cells after the treatment of CCI-779.

Results

mTOR, p70S6K, S6, and 4EBP1 were overexpressed in Bel-7402 cells compared with HL-7702 cells. Bel-7402 cells were sensitive to CCI-779. The survival rate of the cells treated with CCI-779 over 0.312 μM was significantly different compared with that of control (P < 0.05). CCI-779 inhibited the phosphorylation of mTOR (Ser2448), p70S6K (Thr389), S6 (Ser240/244), and 4EBP1 (Thr37/46) in different grades and the expressions of p70S6K, S6, and 4EBP1. As a result, CCI-779 induced a dose-dependent decrease in cell proliferation, G1/S arrest and damage of cell shape.

Conclusions

Taken together, these data showed that CCI-779 can inhibit mTOR signaling and proliferation in Bel-7402 liver cancer cells in vitro. It offers a therapeutic intervention through inhibition of mTOR as a potential strategy for liver cancer.

【 授权许可】

   
2013 Li et al.; licensee BioMed Central Ltd.

【 图 表 】

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