Mechanism of mTOR inhibitors mediated DDP resistance in pancreatic cancer through the mTOR pathway

YULAN PAN, Liuhe Branch of Nanjing Gulou Hospital, Nanjing 211500, PR China, FEI HE, YIYANG ZHANG, CHUNMING FEI
2021 Romanian Biotechnological Letters  
Mechanism of mTOR inhibitor rapamycin mediated cis-Dichlorodiamine Platinum (DDP) resistance in pancreatic cancer was explored. PANC-1, BxPC-3 and SW1990 cells cultured were used for wound healing assay and MTT assay. Western blot was used to see expression levels of mTOR signal pathway associated protein PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR inhibited by rapamycin. The pancreatic cancer cell lines of PANC-1, BxPC-3 and SW1990 were all resistant to DDP. After the application of DDP
more » ... tion of DDP combined with rapamycin, the migration and invasive ability of the three cell lines decreased significantly (P<0.01). Moreover, after different concentrations of rapamycin were added, the survival rate of the three cell lines decreased significantly, so did the IC50 (P<0.01). Western blot assay 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 cells was weaker. Rapamycin can reduce the migration and invasion of pancreatic cancer cells, increase the sensitivity of pancreatic cancer to DDP, and reverse the resistance of DDP. This process is achieved by inhibiting expression and phosphorylation of mTOR signaling pathway related proteins.
doi:10.25083/rbl/26.2/2476.2482 fatcat:i5vsr572dnawtprx3x6f4wn2ki