Knockdown of survivin expression by siRNAs enhances chemosensitivity of prostate cancer cells and attenuates its tumorigenicity.
Survivin, a member of inhibitor of apoptosis family protein, has become an attractive therapeutic target in cancer due to its selective expression in tumor cells and its important roles for tumor cell viability. Here, we show that vector-based small interfering RNAs (siRNAs) silenced survivin expression in prostate cancer cells, resulting in significantly reduced cell proliferation and enhanced apoptosis, and increased the sensitivity of prostate cancer cells (PC-3) to the apoptosis- inducing agent, platinol. Furthermore, PC-3 cells transfected with the siRNA-expressing vector showed lower tumor formation in nude mice xenografts in vivo. These results demonstrated that inhibition of survivin expression by siRNA attenuated the malignant phenotypes of prostate cancer cells, and may provide a novel approach for gene therapy of androgen-independent prostate cancer.
Shen
Jianjun
J
Department of Clinical Laboratory, Xijing Hospital, Fourth Military Medical University, Xioan 710032, China.
Liu
Jiayun
J
Long
Yin
Y
Miao
Yinye
Y
Su
Mingquan
M
Zhang
Qing
Q
Han
Hua
H
Hao
Xiaoke
X
D000728:Androgens / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005240:Feasibility Studies; D005562:Formazans / Q000378:metabolism; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D000077022:Survivin; D013778:Tetrazolium Salts / Q000378:metabolism; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D005562:Formazans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin; D013778:Tetrazolium Salts; C079782:MTT formazan; D002945:Cisplatin