Analysis of resistance-associated gene expression in docetaxel-resistant prostate cancer cells

摘要

Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction. Of the genes implicated in cancer-associated pathways, insulin-like growth factor 1 receptor, DBF4 homolog, sterile α motif and leucine zipper-containing kinase AZK, Patched 1, serpin peptidase inhibitor, clade E, member 1 and breast cancer 2 (BRCA2) were >3-fold upregulated in PC3DR2 cells compared with PC3 cells. BRCA2 knockdown with small interfering RNA decreased the docetaxel resistance of PC3DR2 cells. These results suggest that BRCA2 serves an important role in the docetaxel resistance of prostate cancer cells. In addition, BRCA2 modulation may be a strategy to partially reverse docetaxel resistance in prostate cancer.