异长春花碱对耐顺铂人鼻咽癌细胞多药耐药的逆转作用及其机制  

Reversal Effects and Mechanism of Vinorelbine on the Multi-drug Resistance of Cisplatin-resistant Nasopharyngeal Carcinoma Cell Line

作　　者：韩建庚[1] 

机构地区：[1]天津医科大学附属肿瘤医院药学部,天津300060

出　　处：《中国药房》2014年第1期19-21,共3页China Pharmacy

摘　　要：目的:研究异长春花碱对耐顺铂(DDP)人鼻咽癌细胞(CNE2/DDP)多药耐药的逆转作用及其机制。方法:以对数生长期的CNE2/DDP细胞为对象,检测0.1、1、5、10、50、100μmol/L异长春花碱作用24 h后细胞的增殖抑制率,与空白对照组比较考察5、10μmol/L异长春花碱对细胞耐DDP的逆转倍数(RF)、细胞内罗丹明123的含量、多药耐药基因1(MDR1)、多药耐药相关蛋白1(MRP1)mRNA及其蛋白表达和磷酸化c-Jun氨基末端激酶(p-JNK)蛋白表达、激活蛋白1(AP-1)活性。结果:异长春花碱与剂量呈正相关地抑制CNE2/DDP细胞的增殖;5、10μmol/L异长春花碱对细胞耐DDP的RF分别为2.81、8.38倍;与空白对照组比较,细胞中罗丹明123含量分别提高了2.16和2.79倍(P<0.05),MDR1、MRP1 mRNA及其蛋白,p-JNK蛋白和AP-1活性均明显降低(P<0.05)。结论:异长春花碱可逆转CNE2/DDP细胞对DDP的耐药性,降低细胞中MDR1、MRP1的表达,其机制可能与抑制JNK磷酸化、下调AP-1活性有关。OBJECTIVE： To study the reversal effects and mechanism of vinorelbine on multi-drug resistance of cisplatin-resis- tant nasopharyngeal carcinoma cell line （CNE2/DDP）. METHODS： The inhibitory rate of the proliferation CNE2/DDP cells at loga- rithmic growth phase were detected after treated with 0.1, 1, 5, 10, 50 and 100 μmol/L vinorelbine for 24 h. The reversal fold （RF） of 5 and 10 μmol/L vinorelbine to cisplatin-resistance in CNE2/DDP cell, the contents of intracellular Rh-123, the expres- sions of MDR1, MRP1 and p-JNK and the activity of AP-1 were investigated, compared with blank control group. RESULTS： Vinorelbine could inhibit the proliferation of CNE2/DDP cells in positive dose-dependant manner; 5 and 10 μmol/L vinorelbine re- versed cisplatin-resistance in CNE2/DDP cell with the folds of 2.81 and 8.38, respectively; compared with blank control group, the intracellular contents of Rh-123 was improved by 2.16 and 2.79 fold respectively （P〈0.05） , while the expression of MDR1, MRP1 and p-JNK protein and the activity of AP-1 were decreased significantly （P〈0.05）. CONCLUSIONS： Vinorelbine could re- verse the multi-drug resistance and down-regulate the expression of MDR1 and MRP1, and the mechanism may be associated with the inhibition of JNK phosphorylation and the down-regulation of AP-1 transcriptional activity.

关 键 词：异长春花碱 人鼻咽癌CNE2细胞 顺铂 多药耐药 机制 

分 类 号：R965[医药卫生—药理学]