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Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells
M J Siegsmund1, C Cardarelli, I Aksentijevich
1Laboratory of Molecular Biology, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
The Journal of Urology
|February 1, 1994
Summary
Ketoconazole can overcome multidrug resistance in cancer cells. This antifungal agent shows promise for enhancing chemotherapy efficacy in patients with prostate cancer, as it is safely used in humans.
Area of Science:
- Oncology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- Ketoconazole is an antifungal agent with potential anticancer applications.
Purpose of the Study:
- To investigate ketoconazole's ability to overcome MDR in cancer cells.
- To assess the expression of the multidrug resistance gene (MDR1) in prostate carcinoma tissues.
Main Methods:
- In vitro studies using multidrug resistant KB-V1 cells and parental KB-3-1 cells.
- RNA-PCR assay to detect MDR1 gene expression in 11 prostate carcinoma tissue samples.
Main Results:
- Ketoconazole effectively reversed vinblastine and doxorubicin resistance in KB-V1 cells.
- MDR1 gene expression was detected in 8 out of 11 prostate tumors, suggesting its role in resistance.
- Ketoconazole concentrations used were within safe in vivo limits.
Conclusions:
- Ketoconazole demonstrates potential in overcoming MDR in cancer.
- The findings suggest ketoconazole could be a valuable adjunct to chemotherapy for prostate cancer patients with MDR.