| Abstract: |
The interaction of cis-diamminedichloroplatinum (cisplatin) and a-difluoromethylornithine (DFMO) has been previously shown by us to be roughly additive in enhancing the growth-inhibitory effects of cisplatin and by another group of investigators to be antagonistic. Since two different schedules of administration were used, we sought to investigate systematically the role of schedule dependence in the interaction of cisplatin and DFMO in a panel of pancreatic adenocarcinoma cell lines (PANC-1, of human origin, and WD PaCa and PD PaCa, both of hamster origin). Dose-effect relationships of single drug alone and in combination were analyzed by the median-effect principle and by the combination indices for the quantitation of synergism or antagonism with the aid of a microcomputer. Pre-cisplatin administration of DFMO for 2 or 5 to 6 days at concentrations of 50 or 100 μg/ml (0.21 or 0.42 MM) was found to antagonize the effects of cisplatin to various degrees in the cell lines. In contrast, whenever post-cisplatin DFMO was administered, marked enhancement, which was synergistic in most instances, of cisplatin's inhibition of colony formation was found. Thus, the interaction of cisplatin and DFMO is felt to be schedule dependent with deleterious effects found only when DFMO is administered prior to and not following cisplatin. Furthermore, the combination shows promise as an approach to overcoming drug resistance in pancreatic cancer. © 1987, American Association for Cancer Research. All rights reserved. |
| Keywords: |
cancer chemotherapy; human cell; cisplatin; dose response; pancreas cancer; pancreatic neoplasms; adenocarcinoma; pancreas; animal; cell line; in vitro study; drug resistance; drug synergism; eflornithine; tumor cell line; colony-forming units assay; therapy; pharmacokinetics; drug interaction; hamster; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; support, u.s. gov't, non-p.h.s.; hamsters
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