胶质瘤对MPPa-PDT敏感性研究中ABCG2的作用

发布时间：2018-06-05 16:49

  本文选题：三磷酸腺苷结合转运蛋白G超家族成员 + 焦脱镁叶绿酸甲酯　； 参考：《中国癌症杂志》2017年02期

【摘要】：背景与目的:三磷酸腺苷结合转运蛋白G超家族成员2(adenosine triphosphate-binding cassette superfamily G member 2,ABCG2)在多种肿瘤细胞中表达,能通过外排抗癌药物参与肿瘤耐药。本研究的目的旨在探讨人胶质瘤细胞对焦脱镁叶绿酸甲酯(pyropheophorbide-a methyl ester,MPPa)介导的光动力疗法(photodynamic therapy,PDT)杀伤效应的敏感性及其与ABCG2的关系。方法:选取处于对数生长期的胶质瘤细胞株U87、A172,分别经MPPa-PDT或MPPa-PDT+烟曲霉毒素C(fumitremorgin C,FTC)处理后,采用CCK-8法检测细胞活性;采用蛋白[质]印迹法(Western blot)检测细胞内ABCG2的表达;流式细胞技术法检测未光照前各组细胞内MPPa的含量;AnnexinⅤ-FITC/PI双染流式细胞术检测细胞凋亡率;DCFH-DA染色观察细胞内活性氧(reactive oxygen species,ROS)的产生。结果:MPPa-PDT能抑制A172、U87细胞的活性,且呈一定的光能量依赖性,A172达到半数致死量所需光能量密度为U87的8倍;A172较U87细胞对MPPa-PDT不敏感;A172细胞内高表达的ABCG2影响MPPa在细胞内的聚集;抑制ABCG2后,不仅可以增强MPPa-PDT对A172细胞的杀伤作用,同时可增加MPPa-PDT触发产生的ROS的量及细胞对MPPa的摄取。结论:人胶质瘤细胞株A172对MPPa-PDT相对不敏感,并且产生这种现象的机制可能是ABCG2外排MPPa,减少MPPa的细胞内聚集,进而减弱光敏剂活化后对肿瘤细胞的杀伤作用。
[Abstract]:Background & AIM: adenosine triphosphate binding transporter G superfamily member 2(adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2) is expressed in a variety of tumor cells and can participate in tumor resistance through efflux anticancer drugs. The aim of this study was to investigate the cytotoxicity of human glioma cells to pyropheophorbide-a methyl paraphorbide-a photodynamic therapy (PDT) mediated by pyropheophorbide-a methyl and its relationship with ABCG2. Methods: after treated with MPPa-PDT or MPPa-PDT fumitremorgin Con FTCrespectively, the cell activity was detected by CCK-8 assay, and the expression of ABCG2 was detected by Western blot assay. Flow cytometry was used to detect the MPPA content and Annexin 鈪，

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