Cyclosporin A enhances paclitaxel toxicity against leukemia and respiratory epithelial cancers

Helen J Ross, Andrea L. Canada, Lewis M. Slater

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Multidrug resistance is probably the single greatest obstacle to successful systemic therapy of human cancer. We have reported that cyclosporin A (CsA) can overcome multidrug resistance and improve the efficacy of etoposide in a murine model of drug-sensitive leukemia. The combination of CsA and paclitaxel (PCL) was also significantly superior to either drug alone against murine P388 (sensitive) and L1210 (resistant) leukemia. Lung cancer cells provide an ideal model system to study this phenomenon because both de novo and acquired drug resistance occur. Standard chemotherapy for advanced lung cancer is poorly effective, and although PCL is one of the most active new agents for this disease, responses occur in only 20% of patients. In vitro, CsA significantly enhanced the efficacy of PCL against lung (Lu-CSF-1 and 3LL) and oropharyngeal (CSCC-20) cancer cell lines. The combination also produced an increase in expression of interleukin 1β, a cytokine known to inhibit the growth of Lu-CSF-1 cells. CsA alone had little or no antiproliferative activity in vitro and did not alter PCL transport. These results indicate that the activity of chemotherapy modulators may extend beyond mitigation of drug resistance to enhancement of therapeutic efficacy against drug-sensitive tumor cells in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalClinical Cancer Research
Volume3
Issue number1
StatePublished - 1997
Externally publishedYes

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Paclitaxel
Cyclosporine
Leukemia
Macrophage Colony-Stimulating Factor
Multiple Drug Resistance
Drug Resistance
Lung Neoplasms
Neoplasms
Pharmaceutical Preparations
Leukemia L1210
Drug Therapy
Etoposide
Interleukin-1
Cytokines
Cell Line
Lung
Therapeutics
Growth
In Vitro Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cyclosporin A enhances paclitaxel toxicity against leukemia and respiratory epithelial cancers. / Ross, Helen J; Canada, Andrea L.; Slater, Lewis M.

In: Clinical Cancer Research, Vol. 3, No. 1, 1997, p. 57-62.

Research output: Contribution to journalArticle

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