The dual PI3K/mTOR inhibitor NVP-BEZ235 inhibits proliferation and induces apoptosis of burkitt lymphoma cells.

Abstract

BackgroundPhosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on cell proliferation and apoptosis in Burkitt lymphoma (BL) cells.MethodsTwo human BL cell lines, CA46 and RAJI were used in this study. The proliferation of BL cells was detected by manganese tricarbonyl transfer (MTT) assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels of AKT (Thr308), AKT (Ser473), and RPS6 were evaluated by western blot analysis.ResultsNVP-BEZ235 significantly inhibited the proliferation of BL cells (CA46 and RAJI) and the inhibition effect was time and dose-dependent. Cell cycle analysis indicated that the cells (CA46 and RAJI) were mostly arrested in G1/G0 phase. Cell apoptosis assay showed that the late apoptotic cells were significantly increased after 72 h treatment by 100 nmol/L of NVP-BEZ235. In addition, results also found that NVP-BEZ235 reduced the phosphorylation levels of AKT (Thr308), AKT (Ser473), and PRS6 in BL cells (CA46 and RAJI). Moreover, this inhibition effect on phosphorylation was dose-dependent.ConclusionsNVP-BEZ235 effectively inhibited cell proliferation by G0/G1 cell-cycle arrest and induced apoptosis through deregulating PI3K/Akt/mTOR pathway in BL cells.