Reduced pim-1 expression increases chemotherapeutic drug sensitivity in human androgen-independent prostate cancer cells by inducing apoptosis.

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.

• Authors: Xing Zhang, Yuyan Sun, Peng Wang, Changfu Yang, Shengwei Li
• Journal: Experimental and therapeutic medicine (Exp Ther Med) Vol. 18 Issue 4 Pg. 2731-2738 (Oct 2019) ISSN: 1792-0981 [Print] Greece
• PMID: 31572520 (Publication Type: Journal Article)
• Copyright: Copyright © 2019, Spandidos Publications.