Therapeutic potential of siRNA-mediated combined knockdown of the IAP genes (Livin, XIAP, and Survivin) on human bladder cancer T24 cells.
Livin, X-linked inhibitor of apoptosis (XIAP), and Survivin are three well-known inhibitors of apoptosis almost exclusively over-expressed in cancer cells and are considered potent targets for cancer treatment. In the present study, we found that Livin, XIAP, and Survivin were simultaneously expressed in bladder cancer cells. We speculated that Livin, XIAP, and Survivin might have synergistic effects on cell growth and apoptosis. Our results confirmed that combined knockdown of all these three genes can synergistically inhibit the proliferation and transformation ability of high-grade bladder cancer T24 cells and promote the cell apoptotic sensitivity to chemotherapy. Furthermore, combined knockdown of Livin, XIAP, and Survivin can markedly increase the abundance of active caspase-3, active caspase-7, active caspase-9, and cytosolic Smac. Our findings imply that combined silencing of Livin, XIAP, and Survivin may be a potent multitargeted gene therapy for bladder cancer.
Yang
Deyong
D
Department of Urology, First Affiliated Hospital of Dalian Medical University, China.
Song
Xishuang
X
Zhang
Jianing
J
Ye
Lin
L
Wang
Shujing
S
Che
Xiangyu
X
Wang
Jianbo
J
Zhang
Zhiwei
Z
Wang
Lina
L
Shi
Wei
W
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D000077022:Survivin; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C107489:BIRC5 protein, human; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human