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目的 了解姜黄素与阿霉素联合应用对人口腔上皮癌KB细胞及其多药耐药KBv2 0 0 细胞的杀伤作用及其作用机制。方法 采用MTT法测定药物的体外杀伤作用 ,应用金氏公式进行联合用药分析 ;采用荧光分光光度法进行细胞内阿霉素蓄积测定 ,以荧光探针DPH标记 ,用荧光偏振法测定细胞膜流动性。结果 姜黄素 4 2 5~ 17 0 0 μmol·L-1与阿霉素合用 ,对KB及KBv2 0 0 细胞可产生单纯相加至增强的协同杀伤效果。姜黄素对阿霉素蓄积的影响 ,在KBv2 0 0 细胞显示增加 ,而在KB细胞则显示降低 ;膜流动性实验表明 ,姜黄素对KB及KBv2 0 0 细胞膜流动性均无影响。结论 姜黄素与阿霉素同时联合用药可产生协同作用。其机制在KBv2 0 0 细胞与增加细胞内阿霉素蓄积有关 ;在KB细胞可能与药效协同作用有关 ;但姜黄素对两种细胞的作用均与细胞膜流动性改变无关
Objective To investigate the cytotoxicity of curcumin combined with doxorubicin on human oral carcinoma KB cells and multidrug-resistant KBv2 cells and its mechanism. Methods MTT assay was used to determine the cytotoxicity in vitro. The drug combination was analyzed by King’s formula. The intracellular adriamycin accumulation was measured by fluorescence spectrophotometry. DPH was labeled with fluorescent probe and the cell membrane fluidity was measured by fluorescence polarization. Results The combination of curcumin 4 2 5 ~ 17 0 0 μmol·L -1 with doxorubicin resulted in a simple and additive synergistic killing effect on KB and KBv 2 0 0 cells. The effect of curcumin on the accumulation of doxorubicin showed an increase in KBv2O0 cells and a decrease in KB cells; membrane fluidity experiments showed that curcumin had no effect on the membrane fluidity of KB and KBv2O0 cells. Conclusions Combination of curcumin and doxorubicin can produce synergistic effects. Its mechanism is related to increasing the intracellular accumulation of doxorubicin in KBv2O0 cells; it may be related to synergistic effect in KB cells; however, the effects of curcumin on both cell types are not related to the change of cell membrane fluidity