RESUMO
Resistance to anticancer drugs is one of the major reasons of treatment failure for androgen-independent prostate cancer (PC). Increase in expression of Id-1 has been reported in several types of advanced cancer including PC. It has been suggested that overexpression of Id-1 may provide an advantage for cancer cell survival and thus inactivation of Id-1 may be able to increase the susceptibility of cancer cells to apoptosis. In this study, using small RNA interfering (siRNA) technology, we inactivated the Id-1 gene in two androgen-independent PC cell lines, DU145 and PC3, and investigated whether down-regulation of Id-1 could lead to increased sensitivity of these PC cells to a commonly used anticancer drug, taxol (Tx). Our results showed that inactivation of Id-1 by siId-1 resulted in decrease in both colony forming ability and cell viability in prostate cancer cells after Tx treatment. Furthermore, the siId-1 induced sensitization to Tx was associated with activation of apoptotic pathway. In addition, c-Jun N-terminal kinase (JNK), one of the common pathways responsible for Tx-induced apoptosis, was also activated in the si-Id-1 transfected cells. Inhibition of JNK activity by a specific inhibitor, SP600125, blocked the siId-1-induced sensitivity to Tx. These results indicate that increased Id-1 expression in PC cells may play a protective role against apoptosis, and down-regulation of Id-1 may be a potential target to increase sensitivity of Tx-induced apoptosis in PC cells.
