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1. 重庆市荣昌县人民医院泌尿外科,重庆,402460
2. 重庆医科大学附属第一医院泌尿外科,重庆,400016
纸质出版日期:2015,
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郑 斌, 唐永永, 蒋 立, 等. 婴儿双歧杆菌介导HSV-TK/GCV对前列腺癌PC-3细胞裸鼠移植瘤细胞凋亡的影响[J]. 重庆医科大学学报, 2015,40(10):1347-1351.
Zheng Bin, Tang Yongyong, Jiang Li1, et al. Effects of HSV-TK/GCV suicide gene therapy system mediated by bifidobacterium infantis on cell apoptosis of prostate cancer PC-3 cell xenografts in nude mice[J]. Journal of Chongqing Medical University, 2015,40(10):1347-1351.
郑 斌, 唐永永, 蒋 立, 等. 婴儿双歧杆菌介导HSV-TK/GCV对前列腺癌PC-3细胞裸鼠移植瘤细胞凋亡的影响[J]. 重庆医科大学学报, 2015,40(10):1347-1351. DOI:
Zheng Bin, Tang Yongyong, Jiang Li1, et al. Effects of HSV-TK/GCV suicide gene therapy system mediated by bifidobacterium infantis on cell apoptosis of prostate cancer PC-3 cell xenografts in nude mice[J]. Journal of Chongqing Medical University, 2015,40(10):1347-1351. DOI:
目的:研究婴儿双歧杆菌(bifidobacterium infantis,BI)介导单纯疱疹病毒胸苷激酶(herpes simplex virus thymidine ki-nase,HSV-TK)/丙氧鸟苷(ganciclovir,GCV)自杀基因系统对PC-3细胞裸鼠移植瘤细胞凋亡的影响。方法:采用前列腺癌PC-3细胞悬液皮下注射法建立裸鼠前列腺癌模型,并随机分为4组,每组各12例,分别经尾静脉注射BI-pGEX-TK(重组质粒组)、BI-pGEX-5X-1(空质粒组)、BI(空婴儿双歧杆菌组)和生理盐水(生理盐水组),联合腹腔注射GCV,4周后,称取裸鼠质量及肿瘤质量。TUNEL法检测各组肿瘤细胞凋亡情况,real-time PCR、Western blot分别检测各组肿瘤组织中Fas、FAP-1、casepase3和casepase8的mRNA 及蛋白表达水平。结果:重组质粒组荷瘤裸鼠体质量明显高于其余3组(F=12.952,P=0.000),肿瘤组织质量明显降低(F=7.795,P=0.000);重组质粒组凋亡指数明显高于其他3组(F=45.895,P=0.000);重组质粒组Fas mRNA(F=70.077,P=0.000)、casepase3 mRNA(F=70.611,P=0.000)和casepase8 mRNA(F=73.781,P=0.000)的表达明显上调,FAP-1 mRNA(F=46.880,P=0.000)的表达明显下调。重组质粒组Fas蛋白(F=664.116,P=0.000)、casepase3蛋白(F=203.090,P=0.000)和casepase8蛋白(F=654.354,P=0.000)的表达明显上调,FAP-1蛋白(F=318.989,P=0.000)的表达明显下调。结论:婴儿双歧杆菌介导HSV-TK/GCV自杀基因系统可能通过影响Fas介导凋亡信号通路,诱导荷瘤裸鼠前列腺癌细胞的凋亡,发挥抑癌作用。
Objective:To investigate the effect of bifidobacterium infantis(BI)-mediated herpes simplex virus thymidine kinase(HSV-TK)/ganciclovir(GCV) suicide gene therapy system on cell apoptosis of prostate cancer PC-3 cell xenografts in nude mice. Methods:The prostate cancer model was established by subcutaneous injection of human prostate cancer cell line PC-3 into nude mice. The model mice were randomly divided into 4 groups,which were treated by intraperitoneal injection of GCV in combination with tail vein injection of BI carrying recombinant plasmid BI-pGEX-TK(recombinant plasmid group),BI carrying empty plasmid BI-pGEX-5x-1(empty plasmid group),BI(BI group) and normal saline(normal saline group). After 4 weeks of treatment,tumor weights and nude mice weights were recorded. The apoptosis of tumor was detected by TUNEL assay. The expression of Fas,FAP-1,casepase3 and casepase8 were determined by real-time qPCR and Western blot,respectively. Results:After treatment,comparing with those of empty plasmid group,BI group and normal saline group,the nude mice weights in recombinant plasmid group increased(F=12.952,P=0.000),the tumor weights decreased(F=7.795,P=0.000). The apoptosis index of recombinant plasmid group was obviously higher than that of the other three groups(F=45.895,P=0.000). Comparing with the other three groups,the mRNA expression of Fas(F=70.077,P=0.000),casepase3(F=70.611,P=0.000) and casepase8(F=73.781,P=0.000) in recombinant plasmid group increased,but the mRNA expression of FAP-1(F=46.880,P=0.000) decreased. Protein expression of Fas(F=664.116,P=0.000),casepase3 F=203.090,P=0.000) and casepase8(F=654.354,P=0.000) in recombinant plasmid group increased,but the expression of FAP-1 protein(F=318.989,P=0.000) decreased. Conclusion:The BI-mediated HSV-TK/GCV suicide gene therapy system can inhibit nude mice prostate cancer progression effectively,probably through affecting Fas mediated apoptosis signaling pathways,inducing to nude mice prostate cancer cells apoptosis and playing a role in tumor suppression.
婴儿双歧杆菌前列腺癌单纯疱疹病毒胸苷激酶/丙氧鸟苷Fas
bifidobacterium infantisprostate cancerherpes simplex virus thymidine kinase/ganciclovirFas
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