Study On The Effects And Molecular Mechanism Of Histone Deacetylase Inhibitor MS-275 Inducing Apoptosis In Pancreatic Cancer Cells

Objectives:To investigate the apoptosis-inducing effect of histone deacetylase inhibitor(HDACi) MS-275 on two types of pancreatic cancer cells, and further explore the related molecular mechanism of MS-275’s apoptosis-inducing effect in vitro,to provide an experimental basis for clinical practice of MS-275.Methods:1、Human pancreatic cancer cell line HPAF-Ⅱ、Mpanc 96 were used for this study,pancreatic cancer cells HPAF-Ⅱ and Mpanc 96 were maintained in RPMI1640 supplemented with 10% fetal bovine serum. All cell lines were cultured in a 37oC humidified atmosphere containing 95% air and 5% CO2.The variation in morphology was observed microscopically after the two kinds of pancreatic cancer cells were treated by MS-275.2、The survival rates of HPAF-Ⅱ and Mpanc 96 cells under the treatment of MS-275 were analyzed by MTS assay.Count the IC50 of MS-275 to this two kinds of pancreatic cancer cells.3、The expression of cell apoptosis-related signal pathway protein Akt、pAkt、MAPK、pMAPK、mTOR、pmTOR 、Survivin、PARP and Caspase-3 in HPAF-Ⅱ and Mpanc 96 cells were estimated by Western blotting. Results:Our MTS results showed that the survival rates of both HPAF-Ⅱ and Mpanc 96 were gradually decreased upon treatment with increased concentration of MS-275.The IC50 of MS-275 is1.64uM/Lto HPAF-Ⅱcell and is3.61uM/Lto MPanc 96 cell.The Western Blotting result also showed that MS-275 can lower the phosphorylation level of Akt and mTOR in HPAF- and MPanc 96 cells,which Ⅱhinted that the PI3K/Akt/mTOR signal pathway was specifically interdicted.The expression of Survivin was obviously decreased and the degradation levels of PARP and Caspase-3 were enhanced with time extension under the treatment of MS-275.It verified that MS-275 exhibited time- and dose-dependent cytotoxicity to both HPAF-Ⅱ and Mpanc 96 cells.Conclusion:The MS-275 exhibited time- and dose-dependent cytotoxicity to both pancreatic cancer cells HPAF-Ⅱ and Mpanc 96 in vitro experiment. The mechanism of MS-275 included that, inducing tumor cells’ apoptosis through the way of interdicting the PI3K/AKT/mTOR signal pathway,which decreasing the expression of Survivin and activating Caspase-3.This study constituded the theoretical foundation for development and application of MS-275 as anticancer drugs on pancreatic cancer.