抗癌药合用维拉帕米对体外人胃癌细胞的影响

Combination effects of verapamil with antitumor agents on human gastric carcinoma cell lines in vitro

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- 790 1,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 ,ADM10 μg· L- 1细胞存活率 88% ,CDDP 10 0μg· L- 1 77% ,5 - FU 10 0μg· L- 15 6 % ,合并用药后细胞存活率分别下降至 49% ,47%和 2 9% .其增效倍数为单独用药的 2 .5 1～ 6 .31倍 (P<0 .0 0 1) ,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 。

AIM To study the affect on cells from the antitumor effects of verapamil (VPM) combined with adriamycin (ADM) fluorouracil (5 Fu) and cispatin (CDDP). METHODS MTT assay was used to investigate the cytotoxicity of the drugs against human gastric carcinoma cell line in vitro SGC 7901 individually or in combinations. Light and electron microscopes were employed to observe the changes in morphology of the cell treated with the drugs. Flow cytometry was applied to study the effects of the drugs on the cell cycle of the cell lines. RESULTS VPM significantly decreased the survival level of cells with ADM, CDDP and 5 Fu. Compared with that used individually, the potentiation of the combinations was ranged from 2.51 to 6.31 ( P < 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.