SurvivinT34A突变体对小鼠B16肺转移瘤的治疗作用  

Therapeutic Effects of SurvivinT34A Mutants on Pulmonary Metastases of Melanoma B16 in Mice

作　　者：张琳[1] 李志勇[2] 王春婷[2] 

机构地区：[1]四川大学生命科学学院,成都610064 [2]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）》2011年第3期313-316,共4页Journal of Sichuan University(Medical Sciences)

基　　金：国家重点基础研究发展规划(973)(2006CB504303)资助

摘　　要：目的研究阳离子脂质体介导的Survivin基因负性突变体SurvivinT34A对小鼠B16肺转移瘤的治疗作用,并探讨其作用机理。方法尾静脉接种小鼠黑色素瘤细胞B16建立肺转移模型,接种后第3 d将18只荷瘤鼠随机分为生理盐水组(NS组)、空载体组(pORF9组)和重组质粒pORF9-mSurvivinT34A治疗组(mSurvivinT34A组),尾静脉给药,每次5μg/只(100μL/只),隔天治疗1次,共治疗5次。在接种后第28 d处死全部小鼠,剥离肺组织,称湿重,在显微镜下计数转移灶数量,测量转移灶大小。然后对肺组织进行HE染色观察各组小鼠肺组织病理变化情况,TUNEL染色检测转移灶中肿瘤细胞的凋亡情况。结果与PORF9组和NS组相比,mSurvivnT34A组小鼠肺组织结构基本保持完整,转移灶减少(P<0.05),肺湿重降低(P<0.05),大量肿瘤细胞发生凋亡(P<0.05)。结论 mSurvivnT34A质粒能够显著抑制小鼠黑色素瘤肺转移灶的形成,其作用机理可能主要为诱导肿瘤细胞发生凋亡。Objective To study the antitumor effects and mechanism of cationic liposome-mediated SurvivinT34A mutants in mice with pulmonary metastases of melanoma B16.Methods The pulmonary metastases model of B16,a mouse melanoma cell line,was established by the injection of B16 cell suspension via tail vein of C57BL/6 mouse.3 days later,18 tumor-bearing mice were randomly divided into 3 groups,which were intravenously administrated with normal saline（100 μL）,vector（5 μg DNA,100 μL） and recombinant plasmid SurvivinT34A mutants（5 μg DNA,100 μL） every other day for five doses,respectively.After 28 days,the mice were sacrificed,the lung tissue was weighted,and the number of metastasis foci on lung surface was counted and measured.Then,pathological change of lung tissue was studied with HE stainning.the number of apoptotic cells in tumor tissues was assessed by TUNEL assay.Results Compared with the control,mice treated with mSurvivnT34A had an intact structure of lung,with significant reduction in the number of metastasis foci on lung surface（P〈0.05）,and high level of apoptosis in tumor tissue（P〈0.05）.Conclusion Recombinant plasmid SurvivinT34A mutants（pORF9-mSurvivinT34A） may inhibit the formation of pulmonary metastases of melanoma.

关 键 词：SurvivinT34A突变体 黑色素瘤 转移灶 基因治疗 

分 类 号：R735.9[医药卫生—肿瘤]