Mechanism Of MTOR Inhibitor Regulating Drug Sensitivity Of Pancreatic Cancer

Objective To analyzed the effects of mTOR inhibitors rapamycin（RAPA）on the migration and invasiveness of three cis-Dichlorodiamine Platinum（DDP）pancreatic cancer（PC）cell lines,investigate the Mechanism of RAPA on cis-DDP resistance in pancreatic cancer by mediating the mTOR pathway,and to explore the feasibility of reversing the drug resistance,in order to lay a foundation for the clinical treatment of pancreatic cancer.Methods 3 cisplatin-resistant pancreatic cancer cell lines BxPC-3,PANC-1 and SW1990 were purchased and selected.BxPC-3,PANC-1 and SW1990 were cultured in1×10⁵ U/L 10%fetal bovine serum and RPMI-1640 in an incubator with 5%CO₂ and temperature 37℃.Then the cells in logarithmic growth phase received the various detections:wound healing assay for migration ability;Transwell for invasion ability;MTT for half maximal inhibitory concentration(IC₅₀)after adding rapamycin（0,5,10,20μmol/L）;Western blot for the expression levels of PI3K,p-PI3K,AKT,p-AKT,mTOR,and p-mTOR.To analyze the effects of whether to combine RAPA or not and different concentration RAPA on the migration,invasion and expression of related proteins of pancreatic cancer cells.All data were analyzed by software SPSS 19.0.Results The PANC-1,BxPC-3 and SW1990 were all resistant to cisplatin,which also had strong cell migration and invasion ability when DDP was used,and the IC50 was at high level.After the application of DDP combined with rapamycin,the migration ability and invasive ability of the three cell lines decreased significantly（P<0.01）,moreover,the survival rate of the three cell lines was decreased significantly,so did the IC ₅₀（P<0.01）.Western blot showed that rapamycin significantly down-regulated the expression of PI3K,AKT and mTOR proteins in PANC-1 and BxPC-3 cells,inhibited the phosphorylation of PI3K,AKT and mTOR,decreased p-mTOR protein expression,but its effect on the expression of mTOR protein in SW1990 was weaker.Conclusion Rapamycin can reduce the migration and invasion of pancreatic cancer cells,increase the sensitivity of pancreatic cancer to cisplatin,and reverse the resistance of cisplatin.This process is achieved by inhibiting the expression and phosphorylation of mTOR signaling pathway related proteins.