复方中药紫龙金克服肿瘤细胞多药耐药性的机制  

Mechanism of Chinese Herbal Compound Zilongjin for Antagonizing Multi-drug Resistance of Tumor Cells

作　　者：邹珊珊[1] 徐榕[1] 何琪杨[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050

出　　处：《中国中西医结合杂志》2010年第6期601-606,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金(No.30672482);科技部"重大新药创制"综合性大平台项目(No.2009ZX09301-003)

摘　　要：目的探讨中药紫龙金(Zilongjin,ZLJ)对多药耐药肿瘤细胞的作用机制。方法采用MTT法检测ZLJ对细胞增殖的影响;流式细胞术检测细胞周期以及罗丹明123的荧光强度变化;Western blot方法检测相关蛋白的表达变化。结果 ZLJ分别处理人乳腺癌MCF-7和MCF-7/DOX耐药细胞,以及人口腔上皮癌KB和KBV200耐药细胞。MTT法测定表明:ZLJ作用耐药和敏感细胞的IC50值相近,耐药细胞对ZLJ没有交叉耐药性;无论对敏感和耐药细胞,流式细胞术分析发现ZLJ阻断细胞于S期;ZLJ单独处理MCF-7/DOX和KBV200耐药细胞,可以微弱地降低其耐药性,分别与多柔比星(doxorubicin,DOX)和长春新碱(vincris-tine,VCR)合用,可以明显地增加DOX和VCR的活性;ZLJ处理耐药细胞MCF-7/DOX后,检测到细胞内耐药蛋白P-糖蛋白(P-glyco protein,P-gp)呈时间依赖性降低。Western blot检测表明,ZLJ的抑制作用是通过使凋亡标志蛋白PARP出现切割,启动凋亡通路实现的。结论中药ZLJ抑制耐药细胞增殖,没有交叉耐药性;其抑制作用与诱导细胞凋亡以及降低P-gp表达有关。Objective To explore the mechanism of action of Zilongjin（ZLJ） in antagonizing multi-drug resistance （MDR） of tumor cells.Methods MDR tumor cells,including human breast cancer cell line MCF-7 and MCF-7/DOX,and human oral epithelial cancer cells KB and KBV200,were treated with ZLJ. The inhibition of ZLJ on cell proliferation was determined with MTT assay; cell cycle and fluorescence dye Rhodamine123 intensity were detected by flow cytometry; and the expression of related proteins was examined by Western blot. Results IC50 values in MDR cells after ZLJ treatment were similar to those in sensitive cells; MDR cells showed no cross resistance to ZLJ. Flow cytometric analysis showed that the cell cycles of either sensitive or MDR cells were arrested at S phase after exposure to ZLJ. Using ZLJ singly showed a weak inhibition on MDR of MCF-7/DOX and KBV200 cells,but when used in combining with doxorubicin or vincistine,it evidently increased their cytotoxicity. Expression of P-glycoprotein in MCF-7/DOX cells decreased after ZLJ treatment in a time-dependent manner. Western blot showed that ZLJ could cause the apoptosis marker protein PARP cleavage to initiate the apoptotic pathway.Conclusions The proliferation of tumor cells with MDR could be inhibited by ZLJ and they show no cross resistance to ZLJ. The inhibitory effect is related to the activation of apoptotic pathway and the decrease of P-glycoprotein expression.

关 键 词：多药耐药性 肿瘤细胞 紫龙金 细胞凋亡 中药药理 

分 类 号：R273[医药卫生—中西医结合]