盐酸千金藤素逆转EAC/ADR细胞多药耐药性的作用及其机制

Reversal of multidrug resistance in drug-resistant cell line EAC/ADR by cepharanthine hydrochloride and its mechanism

目的研究盐酸千金藤素对艾氏腹水癌耐药细胞株EAC/ADR多药耐药性的逆转作用及其与核因子κB (NF κB)的关系,探讨其作用机制。方法 MTT法、小鼠移植瘤模型实验观察盐酸千金藤素体外和体内逆转细胞多药耐药性的作用;Dot ELISA法检测细胞核NF κB水平及药物作用后的变化。结果 盐酸千金藤素体外能逆转 EAC/ADR细胞的耐药性,逆转倍数为13倍;体内能延长荷瘤小鼠的生存时间,生命延长率为75.37%;并能降低 EAC/ADR细胞中NF κB的持续性活性及化疗药物对其的激活。结论 盐酸千金藤素具有逆转多药耐药性的作用, 其机制可能与抑制NF κB的活性有关。

Aim To investigate the correlation betw een reversal effect of cepharanthine hydrochloride (CH) on multidrug resistance (MDR) in drug-resistant cell line EAC/ADR and the nuclear transcription factor -κB (NF-κB). Methods Cytotoxicity was determined by the tetrazolium (MTT) as say in vitro. An EAC/ADR cell homograft model was established to investigate the effect of CH on reversing MDR in vivo. The constitutive activity and ac tivation of NF-κB by drugs were measured by Dot-Enzyme-linked Immune Sor bent Assay (Dot-ELISA). Results CH was shown to potentiate the cytotoxicity of ADR, a 1 3- fold reversal effect of resistance was achieved in vitro. In mice bearin g EAC/ADR cell homografts, CH was found to prolong the survival time of animals bearing tumor. Increase in life span over control was 75.37%. In addition, the constitutive activity of NF-κB and activation of NF-κB by chemothera py were lowered by CH. Conclusion The findings suggest that CH is able to reverse drug resistance and its mechanism may be related to suppressing the constitutive act ivity and activation of NF-κB by drugs.