中文摘要：

目的分析肿瘤微环境中异常高表达的白介素6（IL-6）是否可导致间充质干细胞（MSCs）的恶性转化。方法 ELISA法检测肿瘤微环境与正常微环境中IL-6的表达差异。以肿瘤微环境中相应水平IL-6处理的MSCs为实验组,正常微环境中相应水平IL-6处理的MSCs作为正常对照组。采用免疫荧光法检测各组STAT3蛋白表达情况;通过细胞生长曲线观察各组MSCs增殖能力的变化;采用免疫荧光定量PCR和Western blotting检测p53和MDM2的蛋白及mRNA表达变化;通过裸鼠成瘤实验检测各组MSCs的体内成瘤能力。结果肿瘤微环境中IL-6的表达量为191.23±16.80pg/ml,明显高于正常微环境（0.82±0.12g/ml,P〈0.01）。实验组90%±7%的MSCs表达STAT3蛋白,主要集中于细胞核,为激活状态,而对照组未检测到STAT3表达。细胞生长曲线显示,2个月后实验组MSCs生长接触抑制减弱。细胞培养2个月后,与对照组比较,实验组p53蛋白及mRNA表达明显降低（P〈0.01）,MDM2蛋白及mRNA表达明显升高（P〈0.05）。实验组MSCs培养2个月后,接种裸鼠皮下可形成肿瘤,而对照组接种后未见肿瘤形成。结论肿瘤微环境中过表达的IL-6具有促进MSCs恶性转化的作用。

英文摘要：

Objective To analyze whether over expression of IL-6 may promote malignant transformation of rat mesenchymal stem cells （MSCs） in tumor microenvironment. Methods MSCs were divided into two groups： Experimental group （treated with IL-6 in an amount corresponding that found in the tumor microenvironment） and control group （treated with an amount of IL-6 found in normal microenvionment）. The expression of IL-6 was assayed with ELISA in both groups for comparing their difference. The STAT3 protein was determined by immunofluorescence assay. The change in proliferative capacity of MSCs was observed by cell growth curve. The changes in protein and mRNA expressions of pS3 and MDM2 in MSCs were measured by quantitative immunofluorescence-based PCR and Western blotting. Oncogenic rate in nude rat was observed to determine the in vivo oncogenic ability of MSCs. Results IL-6 expression in tumor microenvironment was 191.23＋16.80pg/m1, which was significantly higher than that in the normal microenvironment （0.82 ~ 0.12g/ml, P〈0.01）. STAT3 protein was observed in 90% ~ 7% MSCs in the experimental group, and it was mainly situated in the nuclei, presenting in an activation state, while no STAT3 protein was found in the control group, and there was a significant difference between the two groups （P〈0.01）. Growth curve showed that the contact inhibition of MSCs was attenuated significantly in experimental group two months after cultivation. The expressions ofp53 mRNA and its protein were reduced significantly （P〈0.05）, while that of MDM2 mRNA and protein increased significantly （P〈0.05）, as compared with control group two months after cultivation. Tumor formation was found in experimental group two months after the subcutaneous inoculation of MSCs obtained from the experimental group into nude mice. Conclusion Over expression of IL-6 in the tumor microenvironment may promote malignant transformation of rat bone marrow MSCs.