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

AimTo investigate the correlation between 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). MethodsCytotoxicity was determined by the tetrazolium (MTT) assay 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 activation of NF-κB by drugs were measured by Dot-Enzyme-linked Immune Sorbent Assay (Dot-ELISA). ResultsCH was shown to potentiate the cytotoxicity of ADR, a 13- fold reversal effect of resistance was achieved in vitro. In mice bearing 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 chemotherapy were lowered by CH. ConclusionThe findings suggest that CH is able to reverse drug resistance and its mechanism may be related to suppressing the constitutive activity and activation of NF-κB by drugs.