多柔比星-五味子乙素共载脂质体克服肿瘤多药耐药的研究

Co-Delivery of Doxorubicin and Schisandrin B by Liposome to Overcome Multidrug Resistance

目的探讨五味子乙素与脂质体对克服肿瘤多药耐药的协同作用。方法制备获得多柔比星-五味子乙素共载脂质体,以人白血细胞系K562/DOX耐药细胞为模型细胞,以多柔比星溶液、五味子乙素+多柔比星混合液、多柔比星脂质体、多柔比星脂质体与五味子乙素混合液、维拉帕米+多柔比星混合液为对照,MTT法测定细胞毒性,并测定不同时间点进入耐药细胞的多柔比星量,绘制药物浓度随时间变化曲线。结果多柔比星-五味子乙素共载脂质体逆转倍数分别是五味子乙素、脂质体、多柔比星脂质体与五味子乙素混合液的1.68、14.52和1.42倍。共载脂质体使多柔比星进入耐药细胞的药物量是多柔比星脂质体、五味子乙素的1.30和1.21倍,且具有延缓药物外排作用。结论多柔比星-五味子乙素共载脂质体具备良好的克服肿瘤多药耐药作用,脂质体和五味子乙素显示了良好的协同作用。

OBJECTIVE To investigate the synergetic effect of schisandrin B and liposomes on overcoming multidrug resistance（MDR）.METHODS Co-delivery of doxorubicin and schisandrin B by liposome（DS-L） were prepared,and doxorubicin solution（FDOX）,schisandrin B and doxorubicin mixture（Sch B＋DOX）,doxorubicin liposomes（D-L）,doxorubicin liposomes and schisandrin B mixture（D-L＋Sch B）,verapamil and doxorubicin mixture（Ver＋DOX） were also prepared as the control.The MTT test were measured,and the amount of doxorubicin in the K562/DOX cells at different time were determined,and time course of uptake and efflux were drawn.RESULTS The MTT test shows that the resistance factor（RF） of group DS-L were 1.68,14.52 and 1.42 times of group Sch B＋DOX,group D-L and group D-L＋Sch B respectively.The uptake test shows that amount of doxorubicin of K562/DOX cells in group DSL was 1.30 and 1.21 times of that in group D-L and group Sch B＋DOX respectively.And the efflux test shows DS-L could delay doxorubicin efflux from K562/DOX cells.CONCLUSION The co-delivery of chemotherapeutics and P-gp inhibitors schisandrin B by liposome is a promising approach to overcome MDR.And there is a synergistic effect between liposome and schisandrin B to overcome MDR.