title: Survivin stable knockdown by siRNA inhibits tumor cell growth and angiogenesis in breast and cervical cancers.
abstract: Increased resistance to apoptosis is a hallmark of many tumor cells. Survivin, a member of IAP family protein, is expressed in many human cancers and plays an important role in protecting cells from apoptosis. Here we show that vector-based small interfering RNAs (siRNA) stably knockdown survivin expression in several cancer cell lines, leading to increased apoptotic rate in response to different proapoptotic stimuli, such as doxorubicin or TNF-alpha. The apoptotic susceptibility was dependent on divergent levels of survivin expression. The stable transfectants exhibited abnormal morphology, suppressed cell growth, enhanced spontaneous apoptosis and cell cycle hindrance. Furthermore, in nude mice xenografts of survivin-positive tumors, cells expressing survivin-targeted siRNAs exhibited decreased tumor formation and reduced angiogenesis. Results from these studies: (1) provide direct evidence that intracellular silencing of survivin by siRNA sensitizes human tumor cells to apoptosis; (2) define survivin as a promising molecular target for cancer therapy; and (3) suggest the potential applicability of survivin-targeted siRNA for treating human tumors, probably in combination with chemotherapy.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Qing-Xia
authors.initials: QX
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Jia-Yun
authors.initials: JY
authors.lastname: Liu
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Jia
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Cheng-Ji
authors.initials: CJ
authors.lastname: Wang
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Yao
authors.forename: Si-Yi
authors.initials: SY
authors.lastname: Chen
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000098:blood supply / Q000628:therapy*; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics*; D000077022:Survivin; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin