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Cyclosporin a corrects daunorubicin resistance in ehrlich ascites carcinoma

  • Author(s): Slater, LM
  • Sweet, P
  • Stupecky, M
  • Wetzel, MW
  • Gupta, S
  • et al.
Abstract

We have previously developed a daunorubicin resistant subline of Ehrlich ascites carcinoma (EA/DR) for studies on the reversal of daunorubicin resistance. The mean survival of untreated BALB/c mice bearing drug sensitive parental tumour (EA/DS) is 18.4±0.6 days, mice bearing EA/DS treated with five daily doses of 0.3mgkg-1daunorubicin greater than 60 days, and mice bearing EA/DR treated with the same daunorubicin regimen, 21.1 ± 1.4 days. We now report complete reversal of daunorubicin resistance in EA/DR by cyclosporin A (CsA). The in vitro daunorubicin IC50, defined as that concentration of daunorubicin required to inhibit 50% of DNA synthesis, in EA/DR was 6.7±1.15 μgml-1compared to 2.8±0.72 μgml-1in EA/DS. This value was reduced to 2.8±0.52 and 2.1 ± 10.μgml-1daunorubicin by 3.3 and 13.2 μgml-1CsA respectively, P<0.05. The MST of groups of host mice bearing EA/DR either untreated, treated with five daily doses of 0.3mgkg-1daunorubicin, treated with 80mgkg-1CsA in five divided daily doses or treated with combined daunorubicin-CsA were 19.0±1.0, 21.1±1.4, 24.0±2.6 and >60 days respectively. The mean survival of groups of host mice bearing EA/DR treated with 5mgkg-1or 10mgkg-1CsA simultaneously with daunorubicin for five days was also greater than 60 days. These differences are highly significant. © The Macmillan Press Ltd., 1986.

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