Synergistic effects of cis-platinum and cytosine arabinoside on ovarian carcinoma cell lines, demonstrated by dual-parameter flow cytometry.

Ovarian cancer tends to remain confined to the peritoneal cavity even after widespread dissemination. In order to test the in vitro cytotoxic effect of cis-platinum (CP) and cytosine arabinoside (ara-C), a combination which, in theory, is particularly suitable for intraperitoneal (IP) administration, ovarian cancer cells were exposed to each drug alone and in combination and then sampled serially for 336 hr with cell counts and flow cytometry (FCM). We used dual parameter FCM analysis to study changes in DNA and nuclear protein simultaneously. There was good correlation between the degree of cell kill noted in the counts and the duration of observed cytokinetic disturbances in all the treated series. CP and ara-C alone produced temporary cytotoxic and cytokinetic changes. Together, the two agents produced an enhanced CP effect which lasted 336 hr and was accompanied by continued evidence of cell kill in the counts. We conclude that CP and ara-C in vitro act synergistically on ovarian cancer to achieve a high level of cell kill after a single simultaneous application.