Suppression of livin gene expression by siRNA leads to growth inhibition and apoptosis induction in human bladder cancer T24 cells.
Apoptosis deficiency is a hallmark of many cancer cells. Functional suppression of specific antiapoptotic factors might provide a feasible strategy in cancer gene therapy. Livin, the latest found inhibitor of apoptosis protein (IAP) family member, plays important role in cell growth and apoptosis. It has been reported that Livin is highly expressed in bladder cancer tissues. In this study, we found that, unlike other cancer cell lines, there was only Livin-alpha not Livin-beta expression in bladder cancer cell lines. We further investigated the effects of Livin knockdown on human bladder cancer T24 cell growth and apoptosis. We found that small interfering RNA (siRNA) mediated Livin suppression significantly inhibited T24 cell proliferation and colony formation ability. Livin knockdown dramatically increased the T24 cell apoptotic rate in response to different proapoptotic stimuli, such as Mitomycin and TNF-alpha, and this was associated with caspase-3 and caspase-9 activation. These results suggest that Livin knockdown can inhibit cell growth and increase sensitivity to apoptotic stimuli, and might serve as a potent target in bladder cancer gene therapy.
Yang
Deyong
D
Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, 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
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000172:deficiency* / Q000235:genetics*; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D020169:Caspases