Side populations of glioblastoma cells are less sensitive to HSV-TK/GCV suicide gene therapy system than the non-side population

Side populations of glioblastoma cells are less sensitive to HSV-TK/GCV suicide gene therapy system than the non-side population
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胶质母细胞瘤细胞的侧群对 HSV-TK/GCV 自杀基因治疗系统的敏感性低于非侧群

DOI:
10.1007/s11626-010-9274-6
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发表时间:
2010-06-01
影响因子:
2.1
通讯作者:
Liu, Weiguo
Liu, Weiguo
中科院分区:
生物学4区
文献类型:
--
作者:
Hu, Weiwei;Liu, Weiguo

文献摘要

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胶质母细胞瘤细胞的侧群基本上由于ABCG 2介导的小分子药物外排而对化疗具有抗性。单纯疱疹病毒胸苷激酶/更昔洛韦自杀基因治疗系统是恶性肿瘤包括胶质母细胞瘤的最佳特征策略之一。由于这个系统涉及一种小分子药物更昔洛韦,我们想知道胶质母细胞瘤侧群细胞是否能够“泵出”更昔洛韦,从而对这种自杀基因疗法产生抗药性。通过3-(4,5-二甲基噻唑-2-基)-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四氮唑的检测,我们发现侧种群比非侧种群对该系统的抗性更强。通过流式细胞术和竞争实验,我们发现更昔洛韦是ABCG 2的底物。
Side populations of glioblastoma cells are resistant to chemotherapy basically due to ABCG2-mediated efflux of small-molecule drugs. The herpes simplex virus thymidine kinase/ganciclovir suicide gene therapy system is one of the best-characterized strategies for malignant tumors including glioblastoma. Since this system involves a small-molecule drug ganciclovir, we wonder if glioblastoma side population cells are able to “pump out” ganciclovir and thus resistant to this suicide gene therapy. By 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, we found that side populations are more resistant to this system than non-side populations. By flow cytometry and competition assay, we found that ganciclovir is a substrate for ABCG2.