榄香烯乳剂对肺癌A549/DDP细胞株耐药逆转作用及其机制  

The effect of elemene on reversal multidurg resistance and the expression of P-glyco-protein in A549/DDP

作　　者：姚成才[1,2] 涂远荣[2] 杜好信[1] 姜杰[3] 耿国军[1] 张义[1] 陈隽鹏[1] 陈端扬[1] 叶社房[4] 

机构地区：[1]福建中医药大学厦门中医院胸外科,福建厦门361009 [2]福建医科大学附属第一医院胸外科,福建福州355000 [3]厦门大学附属第一医院胸外科,福建厦门361001 [4]厦门大学分子生物学与材料学院,福建厦门361003

出　　处：《现代肿瘤医学》2013年第12期2670-2673,共4页Journal of Modern Oncology

基　　金：福建省自然科学基金面上项目(编号:2010D014)

摘　　要：目的:探讨榄香烯乳(elemene,ELE)逆转人肺腺癌A549/DDP细胞株耐药性及其机制。方法:采用MTT法检测榄香烯乳单用的细胞毒作用及与顺铂(cisplatin,DDP)合用时耐药逆转作用;采用流式细胞术检测榄香烯乳对A549/DDP细胞内罗丹明-123(rhodamine-123,Rh123)蓄积的影响;采用Western blot检测榄香烯乳对耐药细胞A549/DDP细胞膜上P-gp蛋白表达的影响。结果:不同浓度榄香烯对A549/DDP细胞均有一定的抑制作用,呈时间-剂量依赖性效应。单用DDP的IC50为15.46μg/ml,合用20μg/ml榄香烯24h,IC50为4.15μg/ml,逆转耐药倍数为3.63。同时,榄香烯增加A549/DDP细胞内Rh123的蓄集,降低细胞膜上Pgp的表达,且呈剂量依赖性,表明榄香烯能减少A5 4 9/DDP细胞对药物的外排和抑制P-gp蛋白的表达。结论:榄香烯在体外逆转肿瘤细胞耐药性可能与其抑制P-gp的功能和表达有关。Objective：To investigate the elemene （ELE） reversal of human lung adenocarcinoma A549/DDP cell resistance and its mechanism. Methods： Cytotoxicity of ELE alone or in combination with DDP in A549/DDP cells was determined by MTY assay. Based on flow cytometric technology, the effect of ELE on the uptake of rhodamine - 12 3 （ Rho 12 3 ） in A5 4 9 / DDP cells was detected by measuring Rho123 mean fluorescence intensity （MFI）. P - gp protein expression on the A549/DDP cell membrane were detected by Western blot. Results：Different concentration elemene inhibited the A549/DDP cell proliferation in a time - dose - dependent manner （ P 〈 0.05 ）. Alonely used DDP, IC50 was 15. 46μg/ml ; combined 20μg/ml elemene for 24h, DDP IC50 was 4.15 μg/ml, the reversal activity was 3.63 times higher than that of DDP. Elemene increased intracellular accumulation of Rh123 of the A549/DDP cells, reduced the expression of P- gp on the cell membrane, in a dose -dependent manner, indicating that elemene reduce A549/DDP cells for drug efflux and inhibition of P - gp protein pump function. Conclusion： The reversal activity of DDP is possible related to inhibition of P - gp function and expression in vitro, which lead to an increased intracellular accumulation of anticancer drugs.

关 键 词：肺癌 耐药性 榄香烯 P糖蛋白 A549 DDP细胞株 

分 类 号：R730.53[医药卫生—肿瘤] R734.2[医药卫生—临床医学]