抗癌药合用维拉帕米对体外人胃癌细胞的影响_医学论文.docVIP

抗癌药合用维拉帕米对体外人胃癌细胞的影响_医学论文 抗癌药合用维拉帕米对体外人胃癌细胞的影响_医学论文 【关键词】 胃癌 　　关键词: 胃癌维拉帕米药物疗法化疗增敏剂多药耐药性 　　摘 要:目的 观察无毒剂量钙拮抗剂维拉帕米（VPM）与小剂量化疗药阿霉素（ADM）、5-氟尿嘧啶（5-FU）、顺铂（CDDP），合并用药前后对胃癌细胞影响实验研究. 方法 用MTT法观察其对体外培养的人胃癌细胞SGC-7901，在VPM与ADM，5-FU和CDDP合并用药前后对细胞存活率的影响，并通过流式细胞仪检测细胞周期变化，透射电镜观察细胞超微结构变化. 结果 VPM与ADM，5-FU和CDDP合用与单独应用化疗药相比细胞存活率明显下降，ADM10μg#12539L-1 细胞存活率88%，CDDP100μg#12539L-1 77%，5-FU100μg#12539L-1 56%，合并用药后细胞存活率分别下降至49%，47%和29%.其增效倍数为单独用药的2.51～6.31倍（0.001），细胞生长停止在S期，S期数分数为0.48，抑制细胞有丝分裂及DNA合成，细胞超微结构显示:细胞核固缩、空泡形成、微绒毛减少、线粒体及内质网肿胀. 结论 本研究表明无毒剂量VPM与小剂量化疗药合用，可获得化疗药单独用药相同疗效，VPM增加化疗药对肿瘤细胞的细胞毒作用，增加敏感性，减少药物副作用. 　　Keywords:stomach neoplasmsverapamildrug therapychemosensitizersmultidrug resistance 　　Abstract:AIM To study the affect on cells from the antitu-mor effects of verapamil（VPM）combined with adriamycin（ADM）fluorouracil（5-Fu）and cispatin（CDDP）. 　　METHODS MTT assay was used to investigate the cytotox-icity of the drugs against human gastric carcinoma cell line in vitro SGC-7901individually or in combinations.Light and electron microscopes were employed to observe the changes in morphology of the cell treated with the drugs.Flow cy-tometry was applied to study the effects of the drugs on the cell cycle of the cell lines.RESULTS VPM significantly de-creased the survival level of cells with ADM，CDDP and5-Fu.Compared with that used individually，the potentiation of the combinations was ranged from2.51to6.31（0.01）.The growth of cells stopped at Period S.The mitosis and the formation of DNA were restrained.The super-micro structure of cells showed nudeonic shrinkage and necrosis，swelling of mitochondria，dilation of endoplasmic reticulum and so on.CONCLUSION VPM can increase the sensitivity of carcinoma cells to kinds of antitumor drugs，and so reduce their side effects. 　　0 引言 　　化学治疗在胃癌治疗中占有很重要的地位［1-3］ ，但存在着药物毒性以及肿瘤细胞对化疗药物缺乏敏感性或产生多药耐药性（multidrug resistance，MDR）［4-7］ .使得肿瘤常规化疗面临新的挑战.近年来国外学者做了很多研究工作，其中钙拮抗剂（calci-um antagonist，CA）作为化疗增敏剂引起人们极大兴趣.我们应用MTT法、光镜、电镜、流式细胞仪，观察无毒剂量VPM与小剂量化疗药合