中文摘要：

目的探讨大鼠骨髓间充质干细胞（BMSCs）在肿瘤微环境中是否获得肿瘤细胞的相关生物学特性而导致恶性转化.方法通过6孔板结合Transwell小室建立间充质干细胞和大鼠C6胶质瘤细胞的共培养体系,以共培养组为实验组,另设单独培养的间充质干细胞作为对照组.于相差显微镜下观察培养后两组细胞的形态学改变;采用流式细胞术（FCM）分析细胞周期变化;采用荧光定量PCR和免疫荧光法检测间充质干细胞mdm2、p53mRNA水平及共培养后两组细胞中p53突变蛋白和mdm2癌蛋白的表达.结果共培养后实验组细胞表现为胶质瘤细胞样形态.细胞周期检测结果显示共培养7d后,对照组G1期细胞占90.48%±6.62%,实验组占82.22%±2.74%,两组间差异无统计学意义（P〉0.05）;对照组S期细胞占4.66%±4.16%,实验组占7.35%±1.93%,两组间差异亦无统计学意义（P〉0.05）.定量PCR及免疫荧光检测显示,实验组p53mRNA水平明显降低,为对照组的0.24倍（P〈0.05）;部分实验组细胞（24.8%）中表达突变型p53蛋白,而对照组无突变p53蛋白表达（P〈0.05）.实验组mdm2mRNA及其蛋白的表达水平均明显高于对照组（P〈0.05）.结论肿瘤微环境使大鼠骨髓间充质干细胞获得了肿瘤细胞的相关生物学特性.

英文摘要：

Objective To study whether rat bone marrow-derived mesenchymal stem cells might obtain tumor characteristics and andergo malignant transformation when exposed to tumor microenvironment.Methods A co-cultured system including rat bone marrow-derived mesenchymal stem cells and C6 glioma cells was established by using six-plate and transwell chamber.Mesenchymal stem cells were divided into two groups：experimental group and control group.The mesenchymal stem cells in experimental group were co-cultured with C6 glioma cells,and in control group were cultured alone.The morphological changes in the cells were observed by phase-contrast microscopy.The cell cycle of mesenchymal stem cells was determined by flow cytometry.p53 and mdm2 mRNA were examined by real-time quantitative PCR.The expression of mutational p53 protein and mdm2 protein was detected by immunofluorescence method.Results Cells in experimental group showed glioma-like morphology after being co-cultured for 7 days.The proportion of G1 phase cells in experimental group and control group was 82.22%±2.74% and 90.48%±6.62%,respectively,while the proportion of S phase was 7.35%±1.93% and 4.66%±4.16%,respectively.No significant difference existed between the two groups（P〉0.05）.The level of p53 mRNA in experimental group decreased compared with that in the control group（P〈0.05）.A part of cells（24.8%）in experimental group expressed mutant p53 protein,but there was no mutant p53 protein in control group（P〈0.05）.The expressions of mdm2 mRNA and protein in experimental group significantly increased compared to that in control group（P〈0.05）.Conclusions Tumor microenvironment can motivate rat bone marrow-derived mesenchymal stem cells to obtain tumor characteristics,which provide a preliminary experimental basis for a sound clinical application of mesenchymal stem cells.