Knockdown of HSF1 sensitizes resistant prostate cancer cell line to chemotherapy

Abstract

The treatment of prostate cancer patients usually starts with androgen ablation and followed by chemotherapy; however, in some cases the tumor develops resistant phenotype. Combination therapy is currently regarded as a cornerstone in cancer therapy to overcome the drug resistance. Herein, we investigated the combinatory effect of Docetaxel and Trastuzumab with a novel nanomedicine, BCc1. Also, we knocked down the expression of Heat shock factor-1, HSF1, in resistant Prostate Cancer cell line 3, PC3, using RNA interference, RNAi, to sensitize the cancer cells to the drug treatment. We observed down-regulation of Erb-B2 Receptor Tyrosine Kinase 3, ERBB3, B-Cell Leukemia/Lymphoma 2, BCL2, and Heat Shock Protein 90, HSP90, in HSF1 knockdown PC3 cells. Knockdown of HSF1 made PC3 cells more susceptible to Docetaxel treatment. Additionally, BCc1 nanomedicine was tested on prostate cancer cell line PC3 for the first time. It resulted in reduced metabolic activity in these cells. We propose that a combination of the gene therapy and the chemotherapy gives more favorable results in the treatment of refractory prostate cancer.