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Her-2/neu siRNA表达质粒对前列腺癌裸鼠移植瘤生长的影响
基金项目:,江苏省135工程医学重点学科基金,人事部留学回国人员科技活动项目择优资助经费启动类项目,南京市医学科技发展项目计划
摘    要:目的 观察Her-2/neu siRNA表达质粒对前列腺癌裸鼠移植瘤生长的影响.方法 40只裸鼠皮下接种人前列腺癌PC-3M细胞,分成4组,每组10只.于形成的肿瘤内分别注射转染试剂FuGene HD与Her-2/neu siRNA表达质粒(A组)或无关非同源性序列质粒(B组)的复合物、转染试剂FuGene HD(C组)及生理盐水(D组),每周给药1次,连用4周.首次给药4周后取出肿瘤,测量肿瘤长短径及重量,流式细胞术检测肿瘤细胞周期及细胞凋亡,免疫组化方法 检测肿瘤组织中核增殖抗原(Ki67).结果 A组裸鼠移植瘤体积及重量均明显低于其它三组,凋亡指数显著高于其它三组(P<0.05).A组肿瘤细胞增殖指数显著低于C组(P<0.01).A组肿瘤组织中Ki67阳性的细胞数明显少于其它三组(P<0.01).结论 Her-2/neu siRNA表达质粒对裸鼠前列腺癌移植瘤的生长有抑制作用,并显著促进移植瘤细胞的凋亡.

关 键 词:前列腺肿瘤  基因治疗  Her-2/neu  核糖核酸干扰

Effect of Her-2/neu expression on the xenografts in prostate cancer nude mice
Abstract:Objective To investigate the effect of Her-2/neu siRNA expression plasmid on biological features of the xenografts in prostate cancer nude mice. Methods The mice model with the xenografts was established by subcutaneously implantating the prostate cell line PC-3M cells in 40 nude mice, which were divided into 4 groups of A, B, C and D with 10 mice each. The xenografts tumors were injected with the complex of the transfection reagent FuGene HD and Her-2/neu siRNA expression plamid in group A, or random sequences plasmid in group B, with FuGene HD in group C and normal saline in group D weekly for consecutive 4 weeks. On the 4~th week after the first injection, all mice were executed and the xenografts were removed for weighting, cell cycle and cell apoptosis assay by flow cytometry. Immunohistochemial stains on Ki67 were used for evaluating cell proliferatioa Results The values of the size and weight of the xenografts were lower and the apoptosis index was higher in group A than those in the other three groups (P<0. 05). The proliferation index of the tumor cells was lower in group A than that in group C (P<0. 01). The Ki67 immunopositive cells were significantly less in group A than those in group D (P<0. 01). Conclusion Her-2/neu siRNA expression plasmid may significantly inhibit the proliferation of the xenografts and promote the cell apoptosis in PC-3M prostate cancer nude mice.
Keywords:Prostate cancer  Gene therapy  Her-2/neu  RNA interference
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