Sirt1过表达间充质干细胞对小鼠前列腺癌移植瘤生长的影响  

Sirt1-overexpressing mesenchymal stem cells induce immunopotentiation to inhibit prostate tumor growth in mice

作　　者：郭维[1] 林睿[1] 张鸿翔[1] 张庆云[1] 韩志鹏[2] 宗晨[2] 李蓉[2] 赵秋东[2] 赵雪[2] 周杨[1] 程继文[1] 

机构地区：[1]广西医科大学附属肿瘤医院泌尿外科,南宁530021 [2]第二军医大学附属东方肝胆外科医院肿瘤与免疫实验室,上海200082

出　　处：《中国癌症防治杂志》2017年第2期124-128,共5页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：国家自然科学基金资助项目(81660424)

摘　　要：目的探讨沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog 1,Sirt1)过表达的间充质干细胞(mesenchymal stem cells,MSCs)对小鼠前列腺癌移植瘤生长的影响及其可能的机制。方法通过Sirt1腺病毒载体转染MSCs,构建过表达Sirt1的MSCs,Western blot检测Sirt1的表达。将前列腺癌RM-1细胞分别连同过表达Sirt1的MSCs(RM-1+MSCs-Sirt1组)、经绿色荧光蛋白(green fluorescent protein,GFP)修饰的MSCs(RM-1+MSCs-GFP组)或未修饰的MSCs(RM-1+MSCs组)移植到C57BL/6小鼠腋窝皮下,建立小鼠前列腺癌皮下移植瘤模型,以未经处理的MSCs为空白对照组,RM-1细胞单独移植为对照组(RM-1组)。观察小鼠肿瘤生长情况,第10天处死小鼠,称取瘤重。获取肿瘤组织,流式细胞术检测自然杀伤细胞(natural killer cell,NK)百分数。结果成功建立了过表达Sirt1的MSCs细胞株,实验结束时,所有小鼠均存活。空白对照组小鼠实验全程未见成瘤,其余各组小鼠成瘤率为100%。实验结束时,RM-1+MSCs组、RM-1+MSCs-GFP组和RM-1+MSCs-Sirt1组小鼠皮下肿瘤重量分别为(1.51±0.06)g、(1.58±0.05)g和(0.71±0.04)g,与RM-1组的(1.10±0.05)g比较,差异均有统计学意义(P<0.05)。RM-1+MSCs-Sirt1组移植瘤组织中NK细胞数量显著高于RM-1+MSCs-GFP组、RM-1+MSCs组和空白对照组,差异均有统计学意义(P<0.05)。结论过表达Sirt1的MSCs可抑制小鼠前列腺癌皮下移植瘤生长,机制可能是过表达Sirt1的MSCs可募集更多的NK细胞,从而增强对肿瘤细胞的免疫杀伤作用。Objective To explore changes in prostate cancer tumor growth following treatment with mesenchymal stem cells （MSCs） modified with Ad＊Sirt1,and to analyze the possible mechanism. Methods MSCs modified with Ad-Sirt1（MSCs-Sirt1） or with Ad-GFP （MSCs-GFP） and then mixed with RM-l cells from C57BL/6 mice were subcutaneously administered into the armpit area of C57BL/6 mice in order to establish a tumor-bearing mouse model and detect tumor growth. Natural killer（NK） cells were detected in the tumor regions of the mice. Results All mice survived until they were sacrificed on day 10 after subcutaneous injection. There was no tumor formation when MSCs were injected alone,while tumor incidence was 100% for other groups. In a tumor-bearing mouse model,the relative tumor weight of prostate cancer cells pretreated with MSCs-Sirt1,MSCs-GFP or MSCs was,respectively,（0.71±0.04）,（1.58±0.05） and（1.51±0.06） g. These weights were significantly different from that in the control group （1.10±0.05 g,P〈0.05）. Levels of NK cells in tumor regions were dramatically higher in mice treated with MSCs-Sirt1 and RM-1 than in control mice or mice treated with MSCs-GFP or MSCs（P〈0.05）. Conclusions MSCs modified with Ad-Sirt1 can effectively inhibit prostate cancer cell growth. The reason may be that NK cells accumulate in the inflammatory tumor microenvironment.

关 键 词：前列腺肿瘤 移植瘤模型 间充质干细胞 沉默信息调节因子2相关酶1 自然杀伤细胞 

分 类 号：R737.25[医药卫生—肿瘤]