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作 者:顾兵[1] 曹风军 戈伟[1] GU Bing;CAO Fengjun;GE Wei(Center of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China;Center of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China)
机构地区:[1]武汉大学人民医院肿瘤中心,武汉430060 [2]湖北医药学院附属人民医院肿瘤中心,十堰442000
出 处:《医药导报》2017年第11期1255-1259,共5页Herald of Medicine
摘 要:目的研究盐酸二甲双胍对人宫颈癌Hela细胞株的体外放射增敏作用及其机制。方法克隆形成法检测盐酸二甲双胍放射增敏作用及给药时序、浓度的影响;流式细胞法检测细胞周期分布;4',6-二脒基-2-苯基吲哚(DAPI)染色镜下观察法检测细胞凋亡情况;Western blotting法检测血管内皮生长因子(VEGF)蛋白表达。结果盐酸二甲双胍与放射线联合作用后细胞存活率均较单纯放射组明显降低(P<0.05),不同浓度、不同时序处理,细胞存活率差异有统计学意义,先照射后给药效果优于先给药后照射(P<0.05);盐酸二甲双胍与放射线均能将Hela细胞阻滞于G2/M期,联用阻滞效果更加显著(P<0.01);盐酸二甲双胍与放射线均能破坏细胞核,联用后细胞核皱缩、碎裂现象更加显著;盐酸二甲双胍与放射线单独及联用均能下调VEGF蛋白表达(P<0.05)。结论盐酸二甲双胍可通过阻滞宫颈癌Hela细胞周期于G2/M期、下调VEGF蛋白表达来诱导细胞发生凋亡并增强其对放射线的敏感性。ObjectiveTo investigate the enhancing radiosensitization effect of metformin on cervical cancer Hela cell and to explore its mechanism.MethodsThe radiosensitization effect was observed by Clone forming assay;Hela cell cycle distribution was detected by flow cytometry method;Apoptotic changes was measured by fluorescence microscope and DAPI(4',6diamidino2phenylindole)staining;The expression of vascular endothelial growth factor(VEGF)protein was detected by Western blotting.ResultsCompared with radio alone,the cell survival rate was reduced either by combination with metformin or by metformin alone(P<0.05).The cell survival rate also depended on drug by various schedules and drug concentration(P<0.05).Metformin alone or combined with radiation could arrest cell cycle in G2/M phase(P<0.01),induce cell apoptosis.The levels of protein of VEGF was decreased by metformin,radiation alone or combination(P<0.05).ConclusionMetformin has a radiosensitization effect on Hela cell cultured in vitro,which may be related to arresting in G2/M phase,inducing cell apoptosis and down regulating the level of VEGF protein.
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