The novel mTOR inhibitor CCI-779 temsirolimus induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cellsReportar como inadecuado




The novel mTOR inhibitor CCI-779 temsirolimus induces antiproliferative effects through inhibition of mTOR in Bel-7402 liver cancer cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cancer Cell International

, 13:30

First Online: 28 March 2013Received: 28 January 2013Accepted: 20 March 2013

Abstract

BackgroundLiver 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.

MethodsThe 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.

ResultsmTOR, 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.

ConclusionsTaken 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.

KeywordsCCI-779 temsirolimus mTOR signaling Cell growth Liver cancer cell AbbreviationsmTORMammalian target of rapamycin

S6Ribosomal protein S6

p70S6Kp70 ribosomal S6 kinase

4EBP1Eukaryotic translation initiation factor 4E-binding protein 1

IRS1Insulin receptor substrate-1

PBSPhosphate-buffered saline

SDSSodium dodecylsulfate

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-13-30 contains supplementary material, which is available to authorized users.

Shuyu Li, Yan Liang contributed equally to this work.

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Autor: Shuyu Li - Yan Liang - Manlin Wu - Xiaojing Wang - Haixia Fu - Yuhao Chen - Zhigang Wang

Fuente: https://link.springer.com/



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