Inhibition of mammalian target of rapamycin signaling by CCI-779 (temsirolimus) induces growth inhibition and cell cycle arrest in Cashmere goat fetal fibroblasts (Capra hircus)

CCI-779(替西罗莫司)抑制哺乳动物雷帕霉素靶标信号传导,导致山羊胎儿成纤维细胞(Capra hircus)生长抑制和细胞周期停滞

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作者:Zhigang Wang, Taodi Liu, Yuhao Chen, Xin Zhang, Mingtao Liu, Haixia Fu, Dongjun Liu

Abstract

The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase. It plays an evolutionarily conserved role in regulating cell growth, proliferation, survival, and metabolism via different cellular processes. The purpose of this study was to explore the inhibitory effects of CCI-779 (temsirolimus), a specific mTOR inhibitor, on mTOR signaling, and examine the mechanism of cell growth suppression by CCI-779 in Cashmere goat fetal fibroblasts (GFb cells). GFb cells were sensitive to CCI-779 and the survival rate of cells treated with >3.0 μM of CCI-779 was significantly reduced compared with the control (p<0.01). CCI-779 inhibited the phosphorylation of mTOR (at Ser2448) and S6 (at Ser240/244), and the expression of mTOR, p70S6K, and S6. Thus, CCI-779 was toxic to GFb cells, and it induced a dose-dependent decrease in cell proliferation and caused G1/S cell cycle arrest. Taken together, these data show that CCI-779 can inhibit mTOR signaling and proliferation in GFb cells in vitro. Therefore, mTOR is an important regulator for GFb cell growth and proliferation.

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