[Circumvention of the intrinsic multidrug-resistance in renal cell carcinoma].
Most of renal cell carcinomas (RCCs) are refractory at the start of chemotherapy. We have demonstrated that the frequently elevated expression of the multidrug resistance gene (MDR) in RCCs is associated with the intrinsic vinca alkaloids and anthracyclines resistance. The preliminary clinical trials using verapamil or amiodarone in combination with vinblastine or doxorubicin to overcome multidrug-resistant (MDR) tumors could not achieve satisfactory results owing to severe cardiovascular toxicities of such reversing agents. In the present study, we studied the sensitizing ability of bis-benzyl-isoquinoline (cepharanthine) and SDB-ethylenediamine (N-1379) in natural MDR kidney cancer cells. Cepharanthine remarkably sensitized vinblastine and doxorubicin sensitivities in those cells with high MDR RNA levels. From a clinical point of view, cepharanthine seems to be a potent and less toxic agent to treat natural MDR kidney cancers.
Kakehi
Y
Y
Department of Urology, National Himeji Hospital.
Segawa
T
T
Hashimura
T
T
Yoshida
O
O
D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D044182:Benzylisoquinolines; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D005029:Ethylenediamines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008875:Middle Aged; D013729:Terpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology / Q000627:therapeutic use; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D004317:Doxorubicin; D005029:Ethylenediamines; D013729:Terpenes; D014747:Vinblastine; C048678:N-solanesyl-N,N'-bis(3,4-dimethoxybenzyl)ethylenediamine; C006947:cepharanthine; D052117:Benzodioxoles