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


CONCLUSIONS
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.
Song
Yu-cheng
YC
Henan Institute of Medical Science, Zhengzhou 450052, China.
Xia
Wei
W
Jiang
Jin-hua
JH
Wang
Qing-duan
QD
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D044182:Benzylisoquinolines; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009368:Neoplasm Transplantation; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D011897:Random Allocation; D031607:Stephania / Q000737:chemistry; D052117:Benzodioxoles
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D016328:NF-kappa B; C006947:cepharanthine; D052117:Benzodioxoles