Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular carcinoma cell lines.

Mitsuhiro Masuda, Manami Shimomura, Ken Kobayashi, Shuji Kojima, Tetsuya Nakatsura

Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.

Oncology reports 2011 Nov

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Dysregulation of the phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway frequently occurs in human tumors, and is therefore considered to be a good molecular target for treatment. In hepatocellular carcinoma (HCC), overexpression of p-Akt and decrease of PTEN expression have been reported. NVP-BEZ235 is a novel dual inhibitor of PI3K and mTOR; however, its effect on HCC has not been documented. Consequently, we investigated the effects of NVP-BEZ235 on the PLC/PRF/5, HLE, JHH7 and HepG2 HCC cell lines in vitro and in vivo. NVP-BEZ235 decreased the levels of p-Akt and p-p70S6K and inhibited cell proliferation in all HCC cell lines in a dose-dependent manner. Flow cytometric analysis revealed that inhibition of cell proliferation by NVP-BEZ235 was accompanied by G1 arrest in all cell lines, and that NVP-BEZ235 induced apoptosis in PLC/PRF/5 and HLE cells. Tumor growth was suppressed without body weight loss when NVP-BEZ235 was orally administered to JHH-7 tumor-bearing mice for 11 days. These results suggest that NVP-BEZ235 is a potential new candidate for targeted HCC therapy.

Citation

Mitsuhiro Masuda, Manami Shimomura, Ken Kobayashi, Shuji Kojima, Tetsuya Nakatsura. Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular carcinoma cell lines. Oncology reports. 2011 Nov;26(5):1273-9