Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells

M. J. Siegsmund, C. Cardarelli, I. Aksentijevich, Yoshikazu Sugimoto, I. Pastan, M. M. Gottesman

Research output: Contribution to journalArticle

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Abstract

The antifungal agent ketoconazole was found to overcome resistance to vinblastine and doxorubicin in multidrug resistant KB-V1 cells in vitro. These cells are several hundred-fold more resistant than the parental cell line KB-3-1. Ketoconazole had little or no effect on the parental KB-3-1 cells. The concentrations used to overcome drug resistance in vitro have already been safely used in vivo for treatment of fungal infections and in the monotherapy of hormone independent prostate carcinomas to block adrenal androgen production. Because of a possible beneficial effect of a combination of ketoconazole and a chemotherapeutic drug in multidrug resistant cancers, we examined a panel of 11 prostate carcinoma tissues for the expression of the MDR1 gene by an RNA-PCR assay. MDR1 expression was detectable, albeit at low levels, in 8 of the 11 tumors, suggesting a possible role of this gene in the drug resistance of prostate carcinomas. Our data suggest that ketoconazole might be useful in overcoming multidrug resistance in concentrations that are achievable in humans.

Original languageEnglish
Pages (from-to)485-491
Number of pages7
JournalJournal of Urology
Volume151
Issue number2
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

KB Cells
Ketoconazole
Multiple Drug Resistance
Prostate
Carcinoma
Drug Resistance
Vinblastine
Mycoses
Antifungal Agents
Doxorubicin
Androgens
Neoplasms
Hormones
RNA
Gene Expression
Cell Line
Polymerase Chain Reaction
Pharmaceutical Preparations
Genes
In Vitro Techniques

Keywords

  • drug resistance
  • glycoproteins
  • ketoconazole
  • prostatic neoplasms
  • tumor stem cell assay

ASJC Scopus subject areas

  • Urology

Cite this

Siegsmund, M. J., Cardarelli, C., Aksentijevich, I., Sugimoto, Y., Pastan, I., & Gottesman, M. M. (1994). Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. Journal of Urology, 151(2), 485-491.

Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. / Siegsmund, M. J.; Cardarelli, C.; Aksentijevich, I.; Sugimoto, Yoshikazu; Pastan, I.; Gottesman, M. M.

In: Journal of Urology, Vol. 151, No. 2, 1994, p. 485-491.

Research output: Contribution to journalArticle

Siegsmund, MJ, Cardarelli, C, Aksentijevich, I, Sugimoto, Y, Pastan, I & Gottesman, MM 1994, 'Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells', Journal of Urology, vol. 151, no. 2, pp. 485-491.
Siegsmund MJ, Cardarelli C, Aksentijevich I, Sugimoto Y, Pastan I, Gottesman MM. Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. Journal of Urology. 1994;151(2):485-491.
Siegsmund, M. J. ; Cardarelli, C. ; Aksentijevich, I. ; Sugimoto, Yoshikazu ; Pastan, I. ; Gottesman, M. M. / Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. In: Journal of Urology. 1994 ; Vol. 151, No. 2. pp. 485-491.
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