1. Cyclosporin A corrects daunorubicin resistance in Ehrlich ascites carcinoma
- Author
-
Slater, LM, Sweet, P, Stupecky, M, Wetzel, MW, and Gupta, S
- Subjects
Reproductive Medicine ,Biomedical and Clinical Sciences ,Pediatric ,Brain Disorders ,Genetics ,Rare Diseases ,Intellectual and Developmental Disabilities (IDD) ,Animals ,Carcinoma ,Ehrlich Tumor ,Cyclosporins ,Daunorubicin ,Drug Interactions ,Drug Resistance ,In Vitro Techniques ,Mice ,Mice ,Inbred BALB C ,Oncology and Carcinogenesis ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - 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 0.3 mg kg-1 daunorubicin 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 micrograms ml-1 compared to 2.8 +/- 0.72 micrograms ml-1 in EA/DS. This value was reduced to 2.8 +/- 0.52 and 2.1 +/- 0.10 micrograms ml-1 daunorubicin by 3.3 and 13.2 micrograms ml-1 CsA respectively, P less than 0.05. The MST of groups of host mice bearing EA/DR either untreated, treated with five daily doses of 0.3 mg kg-1 daunorubicin, treated with 80 mg kg-1 CsA 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 greater than 60 days respectively. The mean survival of groups of host mice bearing EA/DR treated with 5 mg kg-1 or 10 mg kg-1 CsA simultaneously with daunorubicin for five days was also greater than 60 days. These differences are highly significant.
- Published
- 1986