Survivin突变基因抗前列腺癌的体内外研究  

Anti-prostate Cancer Activity of Survivin-T34A Mutant in vitro and in vivo

作　　者：潘黎[1] 彭星辰[1] 袁庆中[1] 冷斐[1] 于丹丹[1] 单艳[1] 李志勇[1] 王春婷[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《四川大学学报（医学版）》2010年第3期390-393,共4页Journal of Sichuan University(Medical Sciences)

摘　　要：目的探讨Survivin负性显性突变体T34A对前列腺癌细胞体内外增殖和凋亡的影响。方法体外实验采用1,2-二油-3-三甲胺基丙烷(DOTAP)+胆固醇(CHOL)阳脂质体包裹Survivin-T34A质粒转染小鼠前列腺癌细胞株TRAMP-C1,通过流式细胞术观察其对培养的TRAMP-C1细胞增殖和凋亡的影响;体内实验则建立TRAMP-C1前列腺癌皮下移植瘤动物模型,将24只雄性荷瘤C57BL/6小鼠随机分为生理盐水组(NS)、空载质粒组(PORF-9-null)和治疗组(Survivin-T34A),尾静脉给药,观察各组肿瘤体积及毒副反应。取各组皮下移植瘤石蜡包埋后进行TUNEL染色并测定肿瘤细胞凋亡率。结果流式细胞术结果显示转染了阳脂质体包裹的Survivin-T34A质粒后的前列腺癌细胞其细胞凋亡率为46%。肿瘤体积测量结果显示Survivin-T34A组的肿瘤体积小于空质粒组及NS组(P均<0.05)。TUNEL染色结果显示,Survivin-T34A组肿瘤细胞凋亡率高于其它两组(P均<0.05)。结论 Survivin-T34A突变体可抑制小鼠TRAMP-C1前列腺癌的皮下移植瘤,其作用机制与Survivin-T34A能特异并高效地促进该肿瘤细胞凋亡有关。Objective To investigate the effect of SurvivinT34A mutant on murine prostate cancer and its apoptosis-inducing efficacy in vivo and in vitro.Methods In vitro,prostate cancer cells TRAMP-C1 were transfected with Survivin-T34A plasmid encapsulated by cationic liposome.The apoptosis of TRAMP-C1 was evaluated with flow cytometry.C57BL/6 mice model with TRAMP-C1 prostate cancer was established.Twenty four male mice with TRAMP-C1 prostate cancers were divided randomly into three groups,which were intravenously injected with normal saline,empty vector PORF-9-null encapsulated by cationic liposome and Survivin-T34A plasmid encapsulated by cationic liposome respectively twice a week for eight doses.The size of tumors was measured and the tumor sections of each group were stained with TUNEL reagent for apoptosis detection.Results An apoptotic index of 46% of TRAMP-C1 transfected with Survivin-T34A plasmid encapsulated by cationic liposome was observed.The tumor volume of Survivin-T34A group of C57BL/6 mice with TRAMP-C1 prostate cancer was far smaller than those in the control groups（P〈0.05） and the tumors treated with Survivin-T34A showed significant increase of apoptosis compared with those of control groups（P〈0.05）.Conclusion Survivin-T34A mutant efficiently inhibits the growth of prostate cancer,which is based on the mechanism of Survivin-T34A mutant inducing apoptosis of tumor cells.

关 键 词：Survivin-T34A 前列腺癌 凋亡 基因治疗 

分 类 号：R737.25[医药卫生—肿瘤]