• Jie Zheng, Xianjin Zou, and Jia Yao.
• Department of Pathology, Jingmen First People's Hospital, Jingmen City, Hubei, People's Republic of China. zhengjie9803@163.com
• Chemotherapy. 2012 Jan 1; 58 (4): 273-81.

BackgroundThe phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a key potential target in breast cancer therapy. Because some cancer cell lines are resistant to mTOR inhibition, we combined the mTOR inhibitor with the PI3K inhibitor and assayed the inhibitory effect of this combination versus that of a single inhibitor.MethodsThe proliferation of MCF7, SK-BR-3, T-47D, and MDA-MB-231 cells was measured by MTT assay in the presence of GDC-0941 and/or rapamycin. Afterwards, we determined the visible changes in signaling in the PI3K/AKT/mTOR pathway by Western blotting.ResultsGDC-0941 exhibited excellent inhibition on MCF7, T-47D and SK-BR-3 cells with different characteristics. In addition, GDC-0941 blocked the feedback of PI3K/Akt through S6K1, resulting in decreased Akt activity by rapamycin activation. The combination of GDC-0941 and rapamycin downregulated the key components of the cell cycle machinery, such as cyclin D1 and upregulated the apoptotic markers.ConclusionOur findings suggest that GDC-0941, either alone or in combination with rapamycin, may serve as a new, promising approach for breast cancer treatment.Copyright © 2012 S. Karger AG, Basel.

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