SENSITIZATION OF HUMAN OVARIAN-CARCINOMA CELLS TO CIS-DIAMMINEDICHLOROPLATINUM(II) BY AMPHOTERICIN-B IN-VITRO AND IN-VIVO

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedic hloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with a mphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 mu M, respe ctively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We pr epared HRA cell-inoculated nude mice as an experimental therapeutic mo del for human advanced ovarian carcinoma, Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mic e died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/k g) alone 4 days after inoculation increased MST by only 1.4 days. Simu ltaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg /kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2. 0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that pl atinum accumulation in tumour tissues in nude mice treated with CDDP a nd AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy w ith CDDP and AMB is effective in an experimental animal model of advan ced ovarian carcinoma.