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[Circumvention of the intrinsic multidrug-resistance in renal cell carcinoma]
Y Kakehi1, T Segawa, T Hashimura
1Department of Urology, National Himeji Hospital.
Abstract:
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.
Insights
Cepharanthine effectively overcomes multidrug resistance (MDR) in kidney cancer cells, sensitizing them to chemotherapy. This agent shows promise as a less toxic option for treating MDR renal cell carcinomas.
Area of Science:
- Oncology
- Pharmacology
Background:
- Renal cell carcinoma (RCC) often exhibits intrinsic resistance to chemotherapy.
- Multidrug resistance (MDR) gene expression is frequently elevated in RCC, contributing to resistance against vinca alkaloids and anthracyclines.
- Previous attempts to reverse MDR using agents like verapamil or amiodarone were limited by severe cardiovascular toxicities.
Observation:
- This study investigated the MDR-sensitizing potential of cepharanthine and N-1379 in naturally occurring MDR kidney cancer cells.
- Cepharanthine demonstrated significant sensitization of vinblastine and doxorubicin in kidney cancer cells with high MDR RNA levels.
Findings:
- Cepharanthine effectively reverses multidrug resistance in kidney cancer cells.
- The agent enhances the sensitivity of MDR kidney cancer cells to common chemotherapeutic agents like vinblastine and doxorubicin.
Implications:
- Cepharanthine presents a potentially potent and less toxic therapeutic option for treating natural MDR renal cell carcinomas.
- Further clinical investigation of cepharanthine is warranted for MDR-rich kidney cancers.