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ABCG2蛋白抑制声动力治疗对体外胶质瘤干细胞的杀伤作用

ISSN号：1003-3289
期刊名称：《中国医学影像技术》
时间：0
分类：R73-36[医药卫生—肿瘤;医药卫生—临床医学] TB559[理学—物理;理学—声学;一般工业技术]
作者机构：[1]重庆医科大学附属第二医院神经外科,重庆400010, [2]重庆市肿瘤研究所超声科,重庆400030, [3]重庆医科大学超声影像学研究所,重庆400010
相关基金：国家重点基础研究发展计划（973计划）项目（2011cB707900）、重庆市卫生局医学科研计划（2012-2-065）.

作者：徐忠烨[1,3], 李小青[2], 陈维福[1], 程远[1], 王志刚[3]

关键词：胶质瘤, 肿瘤干细胞, 声动力治疗, 三磷酸腺苷结合盒转运蛋白G2, Glioma, Tumor stem cells, Sonodynamic therapy, ATP-binding cassette transporter G2

中文摘要：

目的探讨三磷酸腺苷结合盒转运蛋白G2（ABcG2）对声动力治疗（SDT）杀伤体外胶质瘤干细胞（GSCs）的影响及其机制。方法以悬浮培养法自胶质瘤细胞中分离和培养GSCs；以流式细胞术、免疫荧光细胞化学染色方法分析ABCG2蛋白在GSCs上的表达；利用ABCG2蛋白特异性阻断剂Fumitremergin C（FTC）分析其对细胞内声敏剂Photofrin的外排作用；通过检测细胞内ROS产量、细胞存活率、细胞凋亡率，分析FTC对SDT治疗效果的影响。结果成功分离和培养了GSCs；ABCG2蛋白在GSCs上过表达；FTC可抑制ABCG2蛋白对细胞内Photofrin的外排作用；FTC通过提高细胞内Photofrin的浓度而提高细胞内ROS的产量，进而增强SDT导致的细胞存活率下降和凋亡率升高作用。结论ABCG2蛋白在GSCs上过表达；抑制ABCG2蛋白的药物外排作用可提高SDT对GSCs的杀伤作用。

英文摘要：

Objective To explore the inhibition role of ATP-binding cassette transporter G2 （ABCG2） on the lethal effect of sonodynamic therapy （SDT） on glioma stem cells （GSCs）. Methods GSCs were isolated and cultured from glioma cells in the suspend culture medium. The expression of ABCG2 on GSCs was analyzed by flow cytometry and immunocytochemical assay. The exocytosis of ABCG2 on Photofrin were studied by ABCG2 specific inhibitor fumitremorgin C （FTC）. The reactive oxygen species （ROS） production, cell viability as well as cell apoptosis were measured to assess the effect of FTC on SDT. Results GSCs were successfully isolated and cultured, on which ABCG2 was overexpressed demonstrated by flow cytometry and immunocytochemical assay. FTC could effectively inhibit the Photofrin excetion caused by ABCG2. FTC increased ROS production through inhibition of Photofrin excetion, which lead to the enhancement effect on SDT-induced cell viability reduction and apoptosis increase. Conclusion The overexpression of ABCG2 in GSCs results in efflux of Photofrin. ABCG2 specific inhibitor can improve the lethal effect of SDT on GSCs.

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