AIM: To 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-KB (NF-KB). METHODS: Cytotoxicity 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-KB by drugs were measured by Dot-Enzyme-linked Immune Sorbent Assay (Dot-ELISA). RESULTS: CH 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-KB and activation of NF-KB by chemotherapy 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 activity and activation of NF-KB by drugs.
AIM: To 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-KB (NF-KB). METHODS:Cytotoxicity 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-KB by drugs were measured by Dot-Enzyme-linked Immune Sorbent Assay (Dot-ELISA). RESULTS: CH 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-KB and activation of NF-KB by chemotherapy 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 activity and activation of NF-KB by drugs.