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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 investigate the effect of mesenchymal stem cells (MSCs) over-expressing silencing type information regulation 2 homolog 1 (Sirt1) on the growth of transplanted prostate cancer in mice and its possible mechanism. Methods MSCs were transfected by Sirt1 adenovirus vector to construct Sirt1-overexpressing MSCs. The expression of Sirt1 was detected by Western blot. The prostate cancer RM-1 cells were treated with MSCs (RM-1 + MSCs-Sirt1) overexpressing Sirt1, MSCs modified by green fluorescent protein (GFP) or RM- The unmodified MSCs (RM-1 + MSCs group) were transplanted subcutaneously in the armpit of C57BL / 6 mice to establish a subcutaneous xenograft model of mouse prostate cancer. The untreated MSCs were used as a blank control group. RM-1 cells were transplanted as Control group (RM-1 group). Tumor growth observed in mice, mice were sacrificed on the 10th day, weighed tumor weight. Tumor tissues were harvested and the percentage of natural killer cells (NK) was measured by flow cytometry. Results The MSCs cell line that overexpressed Sirt1 was successfully established. All the mice survived the experiment. The blank control group mice experiment did not see tumor formation throughout the rest of the mice into the tumor was 100%. At the end of the experiment, the subcutaneous tumor weights of RM-1 + MSCs group, RM-1 + MSCs-GFP group and RM-1 + MSCs-Sirt1 group were 1.51 ± 0.06 g, 1.58 ± 0.05 g and 0.71 ± 0.04) g, which was significantly different from that in RM-1 group (1.10 ± 0.05) g (P <0.05). The number of NK cells in RM-1 + MSCs-Sirt1 group was significantly higher than that in RM-1 + MSCs-GFP group, RM-1 + MSCs group and blank control group (P <0.05). Conclusion Sirt1-overexpressing MSCs can inhibit the growth of subcutaneous xenografts in mice with prostate cancer. The mechanism may be that Sirt1-overexpressing MSCs can recruit more NK cells and thus enhance the immunosuppressive effect on tumor cells.