Abstract
Chemotherapeutic drug resistance is an obstacle for the successful therapy of prostate cancer. The aim of the present study was to identify the effects of proto-oncogene serine/threonine-protein kinase pim-1 (pim-1) in the proliferation of chemotherapeutic drug-resistant prostate cancer cells. Androgen-independent human prostate cancer cell lines PC3 and DU145 were used in the current study. Cisplatin-sensitive PC3 cells and cisplatin-resistant PC3/DDP cells were used in drug-resistance assays. The expression levels of pim-1, permeability glycoprotein (p-gp), caspase-3 and cleaved caspase-3 were determined using western blotting analysis; pim-1 was knocked down using pim-1-specific short hairpin RNA (shRNA); cell viability was determined using MTT assay and IC50 values of the chemotherapeutic drugs in human prostate cancer cells tested were calculated using GraphPad 5 software. Androgen-independent human prostate cancer cell lines PC3 and DU145 were transfected with pim-1-targeted or control shRNA, and MTT results revealed that pim-1 knockdown significantly inhibited PC3 and DU145 cell viability in a time-dependent manner (P<0.01). Cisplatin-resistant cells PC3/DDP exhibited higher levels of pim-1 and p-gp expression compared with cisplatin-sensitive PC3 cells; and pim-1 knockdown markedly increased chemotherapeutic drug sensitivity in PC3/DDP cells. In addition, pim-1 knockdown increased chemotherapeutic drug sensitivity in PC3/DDP cells. The molecular mechanism of drug sensitivity was discovered to be partly due to pim-1 knockdown, as it significantly increased apoptosis in cisplatin-resistant PC3/DDP cells. The present study may provide a new strategy for the therapy of prostate cancer.