title: Inactivation of ID-1 gene induces sensitivity of prostate cancer cells to chemotherapeutic drugs.
abstract: 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.
authors.affiliation: Cancer Biology Lab, Department of Anatomy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Yong-Chuan
authors.initials: YC
authors.lastname: Wong
authors.forename: Xiao-Meng
authors.initials: XM
authors.lastname: Zhang
authors.forename: Ming-Tak
authors.initials: MT
authors.lastname: Ling
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051798:Inhibitor of Differentiation Protein 1; D034741:RNA, Small Interfering; D048031:JNK Mitogen-Activated Protein Kinases; D017239:Paclitaxel