载阿霉素胶束对乳腺癌多药耐药MCF-7/ADR细胞的逆转作用  

Reversal of drug resistance in multidrug-resistant MCF-7/ADR cells of breast cancer by doxorubicin-loaded micelles

作　　者：谢鑫[1,3] 余敬谋[1] 车向新[1] 刘频健[1] 刘勇华[2] 张磊[1] 

机构地区：[1]江西省系统生物医学重点实验室,九江学院基础医学院,江西九江332000 [2]九江学院附属医院药剂科,江西九江332000 [3]南昌大学基础医学院,江西南昌330006

出　　处：《中国医院药学杂志》2013年第8期597-600,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:81001418);江西省卫生厅科技项目(编号:210112028)

摘　　要：目的:研究载阿霉素的胆固醇修饰乙二醇壳聚糖(DCHGC)胶束对人乳腺上皮细胞癌多药耐药MCF-7/ADR细胞的逆转作用。方法:采用乳化-溶剂蒸发法制备载药DCHGC胶束,利用动态光散射法和透射电镜测定胶束的粒径与形态。用四甲基氮唑蓝(MTT)法测定DCHGC胶束和阿霉素对MCF-7/ADR细胞的毒性作用,流式细胞仪和激光共聚焦显微镜研究DCHGC胶束和阿霉素在细胞内的摄取。结果:DCHGC的载药量为11.1%,包封率为84.4%,粒径是289nm,粒径形态呈球形。DCHGC胶束和阿霉素对MCF-7/ADR细胞在48h的IC50分别是3.922μg.mL-1和19.69μg.mL-1,具有显著统计学意义(P<0.01);DCHGC胶束的逆转倍数为5.02倍。流式细胞仪和激光共聚焦显微镜结果表明载药DCHGC胶束能够显著提高阿霉素在细胞内的摄取。结论:DCHGC胶束可明显提高阿霉素在MCF-7/ADR细胞内的富集,增强药物对肿瘤细胞的杀伤作用,有效逆转肿瘤多药耐药。OBJECTIVE To investigate the reversal effect of doxorubicin loaded cholesterol-modified glycol chitosan （DCH- GC） micelles on drug resistance in multidrug-resistant MCF-7/ADR cells of human breast epithelial carcinoma. METHODS The DCHGC micelles were prepared by an emulsion/solvent evaporation method. The size and shape of the micelles were inves- tigated by dynamic light scattering （DLS） and transmission electron microscopy （TEM）. The cytotoxicity of doxorubicin （DOX） and DCHCd2 micelles against MCF-7/ADR cells was assessed by an MTT-hased assay. Cellular uptake of ITX2HGC micelles and DOX was evaluated by flow cytometry and confocal laser scanning microscopy. RESULTS The loading content and encapsulation efficiency of DCHGC micelles were 11.1% and 84. 4%, respectively. The size of DCHGC micelles was 289 nm in diameter, and the micelies were spherical in shape. The ICs0 values of DCHGC and free DOX in MCF 7/ADR ceils for 48 h were 3. 922 and 19. 69 g. mL-~, respectively, and the results among these two groups exhibited significantly different （P〈0.01 ）. Flow cytometry and confocal laser scanning microscopy confirmed that cellular uptake of DOX was markedly increased by DCH- GC micelles. CONCLUSION DCHGC micelles can notably improve the accumulation of DOX in MCF-7/ADR cells,enhance the killing effect of drug in tumor cells,and effectively reverse the multidrug resistance.

关 键 词：阿霉素 胆固醇修饰乙二醇壳聚糖 胶束 多药耐药 MCF-7 ADR细胞 

分 类 号：R979.1[医药卫生—药品]