舒湘岑(孝感市中心医院药学部，湖北 孝感　432100)



维拉帕米联合抗癌药多西他赛对乳腺癌细胞抑制作用的研究

舒湘岑*(孝感市中心医院药学部，湖北 孝感432100)

DOI10.14009/j.issn.1672-2124.2016.02.018

摘要目的：研究多西他赛与维拉帕米联合应用对多药耐药的人乳腺癌MCF-7/ADR细胞的生长抑制作用。方法：采用噻唑蓝(MTT)法测定药物在体外对MCF-7/ADR细胞的抑制作用，计算半数致死量(IC50值)，并且应用金氏公式进行联合用药的效果分析，此外，还应用流式细胞分析技术进行细胞凋亡和细胞周期的分析。结果：多西他赛联合维拉帕米治疗对人乳腺癌MCF-7/ADR细胞有显著的抑制作用， 抑制率与单一应用多西他赛相比提高了10倍，且IC50值为单独用多西他赛的1/10。金氏公式显示多西他赛与维拉帕米二者联合具有协同作用，细胞周期和细胞凋亡的结果进一步证明二者联用强于单一用药。结论：维拉帕米可以逆转乳腺癌细胞的多药耐药，其与多西他赛联合用药对乳腺癌细胞起到协同作用。

关键词乳腺癌细胞； 多西他赛； 维拉帕米

Research on Inhibitory Effects of Verapamil Combined with Docetaxel on Breast Cancer Cells

SHU Xiangcen(Dept.of Pharmacy，Xiaogan Central Hospital，Hubei Xiaogan 432100，China)

ABSTRACTOBJECTIVE：To investigate the inhibitory effects of verapamil combined with docetaxel on human breast cancer cell MCF-7/ADR.METHODS：MTT assay was adopted to determine the inhibitory effects of verapamil combined with docetaxel on breast cancer cell MCF-7/ADR，IC50value was calculated，Jin’s formula was used to analyze the effect of drug combination therapy. Besides，the apoptosis and cell cycle were analyzed by flow cytometry. RESULTS：The inhibitory effects of verapamil combined with docetaxel in treatment of breast cancer cell MCF-7/ADR is significant， the inhibition ratio of was 10 times higher than that of single docetaxel，the IC50value was 1/10 of single docetaxel. According to Jin’s formula，verapamil combined with docetaxel had strong synergism effects. Moreover，the results of cell cycle and apoptosis also showed that verapamil combined with docetaxel had better effects than docetaxel or verapamil alone. CONCLUSIONS：Verapamil can reverse the multi-drug resistance of breast cancer cells，and when combined with docetaxel can gain the synergistic effects on breast cancer cells.

KEYWORDSHuman breast cancer cells； Docetaxel； Verapamil

随着化疗药物的广泛使用，肿瘤治疗中的多药耐药(multidrug resistance，MDR)问题显得越来越突出，也是目前临床肿瘤治疗中的主要障碍和化疗失败的主要原因之一[1]。肿瘤MDR形成机制非常复杂，药物外排蛋白P-糖蛋白(p-glycoprotein，P-gp)在细胞膜上的过度表达，是已经阐明的多种耐药机理中的主要原因[2]。针对P-gp耐药蛋白和耐药机制，肿瘤MDR的逆转策略主要体现在釆用载体给药系统和多药耐药逆转剂逆转MDR。抗癌药物多西他赛的抗癌谱广，适用于多种恶性肿瘤的治疗，但是MDR限制了其临床应用[3-4]。……