阿霉素脂质体对克服肿瘤多药耐药的细胞学体外评价

Cytological study on the effect of overcoming multidrug resistance of liposomal doxorubicin in vitro

目的:评价市售阿霉素脂质体体外逆转肿瘤多药耐药(MDR)的作用。方法:MTT法比较阿霉素和阿霉素脂质体体外对敏感和耐药细胞的细胞毒作用;荧光显微镜观察2组药物对敏感和耐药细胞的影响;流式细胞仪检测2组分别在细胞内的积累和外排情况。结果:细胞毒性试验结果显示,尽管在敏感细胞中,阿霉素脂质体IC50远高于阿霉素溶液组,对于耐药细胞株,阿霉素脂质体的IC50与游离阿霉素无显著性差异(P>0.05);细胞荧光染色显示,阿霉素脂质体较溶液在耐药细胞核中有更强的红染;细胞摄取试验显示,相同浓度下,阿霉素脂质体较溶液组在耐药细胞中积累量差异无显著性(P>0.05),但外排试验显示,在耐药细胞KBv200中,相同浓度下的脂质体较溶液具有更强的细胞滞留能力(P<0.05)。结论:阿霉素脂质体较阿霉素溶液在体外能更多进入耐药细胞核,并表现出更强的药物滞留能力,可部分克服多药耐药。

OBJECTIVE To investigate the effect of overcoming multidrug resistance of liposomal doxorubicin in vitro.METHODS Different sensitive and resistant cell lines were cultured with various concentrations of liposomal doxorubicin or doxorubicin solution.MTT assay,fluorescence microscopic observation and flow cytometry assay were then used to monitor the growth of the cell lines and drug accumulation and efflux.RESULTS The IC50 of doxorubicin-liposome on sensitive cell lines was higher than free doxorubicin,however,the difference between their IC50 was not significant on resistance cell lines（P〉0.05）;stronger fluorescence in nucleus was found in liposomal doxorubicin treated cells than cells treated with free doxorubicin;more in-depth study revealed that there was no significant difference between KBv200 cells treated with doxorubicin-liposome and free doxorubicin,however,doxorubicin-liposome showed longer retention ability than free drugs in resistant cells（P〈0.05）.CONCLUSION Compared with free doxorubicin,liposomal doxorubicin can partially overcome multidrug resistance in vitro.