Bcl-2在人脑胶质瘤干细胞样细胞中的表达及病理相关性

Bcl-2 expression and its pathological correlation in human glioma stem-like cells

目的检测B细胞淋巴瘤/白血病-2(Bcl-2)基因在胶质瘤干细胞样细胞(GSLCs)中的表达水平,并分析Bcl-2与来源胶质瘤恶性程度的相关性。方法从8例临床标本中培养出GSLCs并鉴定后,检测Bcl-2在GSLCs以及相应原代胶质瘤细胞中的mRNA和蛋白水平并比较分析;此外对GSLCs中Bcl-2水平及来源胶质瘤恶性程度之间的关系进行分析。结果从8例胶质瘤标本中培养出GSLCs并通过鉴定。实时逆转录酶-聚合酶链式反应和酶联免疫吸附试验检测显示Bcl-2在GSLCs中的mRNA和蛋白水平均显著高于对应的原代胶质瘤细胞,配对t检验结果分别为P<0.001和P<0.005,有统计学意义。此外,Bcl-2的在Ⅳ级脑胶质瘤来源的GSCLs中的表达水平明显高于Ⅲ级脑胶质瘤来源的GSCLs。结论首次检测并发现GSCLs中Bcl-2的表达水平高于相应的原代胶质瘤细胞,此结果与胶质瘤干细胞(GSCs)特点相符,这可能是GSCs产生治疗耐受性并逃避凋亡的原因之一。以Bcl-2为靶点的抗肿瘤治疗须能诱导GSCs凋亡,才有望治愈胶质瘤。

Objective To assess the mRNA and protein expression of anti-apoptotic gene, B-cell lymphoma/ leukemia-2 （Bcl-2） in brain glioma stem-like cells （GSLCs）, and to investigate the correlation between Bcl-2 expression in GSLCs and gliona malignancy. Methods GSLCs were cultured from eight clinical specimens, followed by real-time reverse transcription polymerase chain reaction and immunoassay to compare the expression levels of Bcl- 2 in GSLCs and their corresponding primary glioma cells. Furthermore, the correlation between Bcl-2 expression in GSLCs and glioma pathological grades were analyzed. Results Bcl-2 mRNA and protein expression levels were higher in GSLCs than that in their counterparts, and the expression levels were notably up-regulated in GSLCs of grade 1V gliotms rather than grade Ill gliomas. Conclusion As an anti-apoptotie gene, Bcl-2 assigns ＂immortality＂ characteristic to ceils, which is coincident to the pivotal biological feature of glioma stem cells （GSCs）. The experimental results indicate that GSLCs can evade apoptosis for higher Bcl-2 expression, and might interpret the resistance of GSCs to cytotoxic drugs and other proapoptotic agents. New therapies targeting Bcl-2 must induce the apoptosis of GSCs, thus the glioins would be eradicated.