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RNA Interference Mediated Survivin Gene Silence Inhibit Growth Of Prostate Carcinoma Xenograft In Nude Mice

Posted on:2008-08-12Degree:MasterType:Thesis
Country:ChinaCandidate:C TianFull Text:PDF
GTID:2144360218451232Subject:Urology
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Objective: To investigate whether RNA interference mediated survivin gene silence can inhibit growth of prostate carcinoma xenograft in nude miceMethods and materials: Prostate carcinoma PC-3m cells were cultured in vitro and implanted subcutaneously in the right hypochondrium of BALB/C nude mice. After 14days, the xenografts were randomly divided into three groups; control group, negative control group and experiment group. The adenovirus vector loaded with two piece of survivin shRNA was injected directly into xenografts of experiment group once every two days for five times. The volume of xenografts was dynamic observed. After 30 days, the tumor in each group were weighted, the expression of survivin in prostate carcinoma was examined with immunohistochemistry and the ultramicrostructure change occurring in PC-3m cells was observed by the transmission electron microscope (TEM).Results: Routine pathological examination showed that the xenograft model of prostate carcinoma in nude mice was established successfully. After 30days by multiple directions intratumoral injection of survivin shRNA, survivin shRNA effectively inhibited growth of human prostate carcinoma, which was not compared to the negative control group and control group. Survivin expression in cancer tissue of nude mice decreased. The transmission electron microscopic analysis of the ultrastructural changes revealed some morphological changes which included altered cytosolic density, pronounced vacuole formation, chromatin condensation and nuclear fragmentation at the margin of nuclear envelope, the dilation of cytoplasmic organelles such as mitochondria and rough endoplasmic reticulum, and the apoptotic body formation.Conclusion: RNA interference mediated survivin gene silence can effectively inhibit xenograft growth of prostate carcinoma and increase apoptosis of PC-3m cells conspicuously. RNA interference may be a new therapy for advanced prostate cancer.
Keywords/Search Tags:adenovirus vector, survivin, short hairpin RNA, RNA interference, prostate carcinoma, apoptosis
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