叶黄素等天然抗氧化剂逆转MCF-7/ADM多药耐药作用的筛选及机制研究

Drug screening for reversal of multidrug resisitance in human breast carcinoma MCF-7 /ADM cells from natural antioxidants and mechanism research

目的:在多种天然抗氧化成分中筛选人乳腺癌多药耐药细胞MCF-7/ADM的逆转剂。方法:采用MTT法检测天然抗氧化剂单用及联合化疗药物对MCF-7/ADM细胞的毒性;激光共聚焦显微镜技术观察不同浓度(20、40μg/ml)叶黄素与阿霉素共同孵育2h和4h细胞内阿霉素含量变化。结果:无细胞毒剂量下白藜芦醇、原花青素、番茄红素、叶黄素、阿魏酸对阿霉素逆转耐药倍数分别为1.28、1.27、1.43、1.14、1.09。橙皮苷、丹皮酚在出现细胞毒性剂量下仍未出现明显的逆转作用。其中叶黄素在10、20、40μg/ml对MCF-7/ADM的敏感性依次增强,对阿霉素逆转倍数分别为1.11、1.37、2.11;对长春新碱逆转倍数分别为1.24、2.11、2.26。不同浓度叶黄素和阿霉素作用,发现细胞内荧光强度随着浓度的增大而增强,且共育4h细胞内阿霉素荧光强度较共育2h强。结论:脂溶性较好的抗氧化剂白藜芦醇、原花青素、番茄红素、叶黄素和阿魏酸对MCF-7/ADM细胞具有耐药逆转作用;叶黄素具有促进阿霉素内化入细胞的作用。

Objective： To screen new multidrug resistance（ MDR） reversal in human breast carcinoma MCF-7 /ADM cell line from natural antioxidants. Methods： MTT method was used to test the cytotoxicity of natural antioxidants simply or combined with chemotherapeutics in MCF-7 and MCF-7 /ADM cells. LSCM technology at different concentrations lutein（ 20,40μg /ml） incubation 2 and 4 hours together with adriamycin doxorubicin content changes in the cells. Results： Resveratrol,Proantho Cyanidins,Lycopene,Lutein,and Ferulic acid could reverse adriamycin resistance in MCF-7 /ADM cell line with fold-reversal of 1. 28,1. 27,1. 43,1. 14 and 1. 09,respectively. On the contrary,Hesperidin and paeonol could not reverse MDR even in cytotoxic concentration. The fold-reverse was increasing with the concentration increase from 10 to40ug /ml of lutein,and the fold-reverse to ADM was1. 11,1. 37 and 2. 11,and the fold-reverse to VCR was 1. 24,2. 11 and 2. 26,respectively. Different concentrations of lutein and adriamycin,found that the fluorescence intensity in cells increased with the increase of concentration,and produced four hours intracellular adriamycin fluorescence intensity is produced for 2 hours. Conclusion： Resveratrol,proantho cyanidins,lycopene,lutein,and ferulic acid could reverse MDR in MCF-7 /ADM cell line. Lutein could promote the internalization of adriamycin.