小剂量化疗药合用维拉帕米对体外人结肠癌细胞的影响

Effects of verapamil combined with antitumor agents on human colonic carcinoma cell line 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)合并用药前后对结肠癌细胞SW - 480的影响。方法 用MTT法观察其对体外培养的人结肠癌细胞SW - 480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、CDDP、5 -FU合用与单独应用化疗药相比细胞存活率明显下降 ,当ADM 10ng/ml细胞存活率为 81 46 % ,CDDP 10 0ng/ml 80 0 6 % ,5 -FU 10 0ng/ml 5 4 12 % ;合并用药后分别下降至 48 43 % ,49 2 2 % ,30 89%。其增效倍数为单独用药的 2 40～ 3 95倍 (P <0 0 1) ,细胞生长停止在S期 ,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 。

Objective To study the effects of verapamil(VPM) combined with adriamycin(ADM),fluorouracil(5-Fu) and cisplatin(CDDP) on human colonic carcinoma cells.Methods MTT assay was used to investigate the cytotoxicity of the drugs against human colonic carcinoma cell line SW-480 in vitro individually or in combinations.Light and electron microscopes were employed to observe the changes in morphology of the cells treated with the drugs.Flow cytometry was applied to study the effects of the drugs on the cell cycle of the cell line.Results VPM combined with ADM,CDDP and 5-Fu significantly decreased the survival level of the carcinoma cells.Compared with single use of chemotherapeutic agents,the potentiation of the combined use ranged from 2.40 to 3.95(P<0.01).The growth of cells stopped at phase S.The mitosis and the formation of DNA were inhibited.The super microstructure of cells showed nucleonic shrinkage and necrosis,swelling of mitochondria,and dilation of endoplasmic reticulum.Conclusions VPM can enhance the sensitivity of carcinoma cells to varius antitumor drugs and reduce side effects.