Abstract:

Prostate cancer is the most common cancer among men, and developed metastasis spread to parts of the body. Clinically, prostate cancer can develop resistance to chemotherapy drugs, and generally, the initial treatment for metastatic prostate cancer is androgen deprivation therapy in combination with chemotherapy. This study aimed to further investigate the signaling mechanisms of Bicalutamide (BCLT) with TRAIL combination in resistance to Docetaxel (DX) on the prostate cancer cell. The human prostate cancer cell lines PC3 were generated by initially treating with DX for docetaxel resistance prostate cancer cells (PC3/DX). PC3/DX cells were transfected pAR plasmid for modeling androgen-dependent docetaxel resistance prostate cancer cells (PC3/DX/AR+) and were incubated with BCLT (2.5 μM) and/or TRAIL (2.5 ng/mL). After the treatment, cell proliferation was determined with an MTT assay. Apoptotic cells were investigated with AO/EB staining by fluorescence microscope. Levels of Caspase-3, Caspase-8, AR, TNF-α protein and gene expression were evaluated. We found apoptosis increased with TRAIL (5 ng/mL) in PC3/DX cells, whereas with the combination of 2.5 ng/mL TRAIL and BCLT (2.5 μM) in PC3/DX/AR+ cells. TNF-α protein and gene expression levels increase with TRAIL in PC3/DX and PC3/DX/AR+ cells. AR protein and gene expression levels increased with BCLT and TRAIL PC3/DX/AR+ cells. Our results indicate that BCLT and TRAIL combination has potential agents for inhibiting docetaxel resistance prostate cancer growth and metastasis.

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