Antitumor Activity Of A PI3K/MTOR Inhibitor (NVP-BEZ235)Against Thyroid Cancer Depends On Suppression Of Proliferation And Promotion Of Apoptosis

Objectives:To investigate the PI3K/mTOR inhibitor of NVP-BEZ235 on suppression of proliferation and promotion of apoptosis of SW579 cells in vitro.Methods:SW579 cells were treated with NVP-BEZ235 in vitro, and the cells growth and proliferation was detected by using MTT assay. The growth curves were drawn, and screening of drug concentration. NVP-BEZ235 100nM,250μM was added to the cells, and the same amount volume of DMSO was added to the control group. Then after 48 hours, extracted the protein, and Western-blot was used to detect the change of Cyclin A, Cyclin B1 and Cyclin D1. The effect of NVP-BEZ235 on migration ability of SW579 cells in thyroid cancer were detected by scrach test. Meanwhile SW579 cells were treated with NVP-BEZ235, and using Western blot to detecte the expression of the PI3K/mTOR signaling pathway proteins, caspase3, caspase8 and PARP protein. Series of molecular techniques, such as colony formation was used to determine the proliferation in Panc-1 cells with and without treatment.Results:1. NVP-BEZ235 suppressed the proliferation of thyroid cancer SW579 cells in vitro. MTT assays showed that the PI3K/mTOR inhibitor of NVP-BEZ235 suppressed the proliferation of SW579 cells. Western blot indicated that the expression of Cyclin A, Cyclin B1 and Cyclin D1 protein in SW579 cells are decreased with the concentration of NVP-BEZ235 (100nM,250μM) inceased.2. NVP-BEZ235 inhibited e expression of the PI3K/mTOR signaling pathway proteins. The expression of p-Akt, p-S6 and p-4E-BP1 protein in SW579 cells are decreased with the concentration of NVP-BEZ235 (100nM,250μM) inceased. 3. NVP-BEZ235 induces the apoptosis of SW579 cells by activation of caspase-3/8 and PARP in vitro. Western blotting showed that the cleaved caspase-3/8 and PARP protein was significantly increased in the SW579 cells treated by NVP-BEZ235 compared with the control untreated cells.Conclusions:1. NVP-BEZ235 inhibits the growth of thyroid cancer through down-regulating the expression level of cell cycle protein in SW579 cells.2. NVP-BEZ235 maybe induce the apoptosis of SW579 cells via the activation of caspase-3/8 and PARP.3. NVP-BEZ235 can kill the thyroid cancer cells through PI3K/Akt/mTOR signaling pathway in vitro.