维拉帕米介导食管癌细胞多药耐药及细胞凋亡的实验研究  

Experimental study of verapamil mediated apoptosis of esophageal cancer cells and multi-drug resistance

作　　者：翁呈韬[1] 张腾跃[1] 刘亚贝[1] 樊高飞[1] 吴旸[1] 范平生[1] 

机构地区：[1]安徽省肿瘤医院肿瘤内科,安徽合肥230031

出　　处：《实用临床医药杂志》2017年第24期1-5,共5页Journal of Clinical Medicine in Practice

基　　金：国家自然基金(81172364;81201576);安徽省自然科学基金(1408085MH211);安徽省卫生厅重点科研项目(2010A006)

摘　　要：目的探讨维拉帕米提高食管癌化疗药物敏感性及促进细胞凋亡的影响。方法采用CCK-8法检测紫杉醇、顺铂、5-氟尿嘧啶对于4种食管癌细胞系(EC109、EC9706、KYSE-450、TE-1)的IC50值(IC501);用维拉帕米(4.91μg/m L)联合上述化疗药物处理每种细胞,CCK8法检测维拉帕米联合上述化疗药物针对上述4种食管癌细胞株(EC109,EC9706,KYSE-450和TE-1)IC50值(IC502);以前期实验得出的VER逆转化疗耐药能力差异最为显著的一对食管癌细胞为研究对象,Annexin V-PI双染法检测食管癌细胞凋亡。结果紫杉醇在KYSE-450和EC9706的IC50值明显大于EC109和TE-1,顺铂在TE-1细胞中IC50值明显小于其他3种细胞,5-氟尿嘧啶在EC109中IC50值明显高于在其他3种细胞。加用维拉帕米后,4种食管癌细胞系(EC109,EC9706,KYSE-450和TE-1)针对紫杉醇、顺铂、5-氟尿嘧啶的IC50值均不同程度下降,提示维拉帕米均不同程度提高了上述3种化疗药物的敏感性。其中,顺铂组未加入维拉帕米前,EC109,EC9706,KYSE-450与TE-1相比,均存在不同程度耐药性,加入维拉帕米后,针对EC9706 IC50值变化倍数较大(15.2倍),提示逆转敏感;针对EC109IC50值变化倍数较小(1.6倍),提示逆转耐受。结论维拉帕米逆转EC9706的阿霉素效率指数最高(15.2倍),与EC109细胞相比有显著性差异(1.6倍)。提示EC9706(DDP)对维拉帕米的逆转敏感,而EC109(DDP)对维拉帕米的逆转耐受。维拉帕米有可能通过促进细胞调亡途径提高其逆转化疗耐受的能力,从而增强化疗药物敏感性。Objective To investigate the effect of verapamil on chemosensitivity and apoptosis of esophageal cancer cells. Methods The IC50 values （ ICs01 ） of three kinds of chemotherapy drugs ： paclitaxel, cisplatin, and 5-fluorouracil were detected by CCK-8 method in 4 kinds of esophageal cancer cell lines （EC109, EC9706, KYSE-450, TE-1）. Each cell was processed by verapamil （4.91 μg/mL） combined with the chemotherapy treatment above, IC50 （IC502） value was detected by CCK8 assay combined with chemotherapy for the verapamil of the 4 esophageal carcinoma cell lines （ EC109, EC9706, KYSE-450 and TE-1 ）. A pair of esophageal cancer cells with the most significant reversal of the resistance to chemotherapy by VER detected by the previous experiments were included as research objects, and Annexin V-PI double staining method was used to detect the apoptosis of e- sophageal cancer cells. Results The IC50 values of paclitaxel in KYSE-450 and EC9706 cell lines were significantly higher than that in EC109 and TE-1. The ICso values of cisplatin in TE-1 ceils were significantly less than those in the other three ceils, while the IC50 values of 5-fluorouracil in EC109 were significantly higher than that in other three cell lines. After adding verapamil, the IC50 values of paclitaxel, cisplatin and 5-fluorouracil in four esophageal cancer cell fines （EC109, EC9706, KYSE-dS0 and TE-1） all decreased to different degrees, and the above three kinds of chemotherapeutic drugs had increased their sensitivity to varying degrees. Among them, the cisplatin group before adding verapamil had different degrees of resistance compared with EC109, EC9706, KYSE-450, TE-1. After joining verapamil, ICs0 value change for the EC9706 multiplied for 15.2 times, suggesting that the reversal was sensitive; ICs0 value change for EC109 was 1.6 times smaller, suggesting that the reversal was tolerant. Conclusion Verapamil reversal of EC9706 adriamycin has highest efficiency index （15.2 times）, there was significant difference compar

关 键 词：维拉帕米 食管癌 耐药性 逆转能力 细胞凋亡 

分 类 号：R735.1[医药卫生—肿瘤]