Effects of cyclosporin A and alpha-difluoromethylornithine on the growth of hamster pancreatic cancer in vitro.
The growth and survival of hamster H2T pancreatic ductal adenocarcinoma in vitro are known to be significantly reduced by inhibitors of polyamine biosynthesis. alpha-Difluoromethylornithine (alpha-DFMO) is a specific and irreversible inhibitor of ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis. alpha-DFMO treatment inhibits the growth of H2T pancreatic cancer cells and decreases H2T cell survival in vitro and in vivo. In the present study, the effects of cyclosporin A (CsA) were examined on growth, survival, and polyamine levels in H2T pancreatic ductal adenocarcinoma in vitro. CsA had inhibitory effects on H2T pancreatic cancer growth similar to those of alpha-DFMO; these effects were blocked by the addition of the polyamine putrescine. Polyamine levels were found to be significantly altered in cells treated with CsA and/or alpha-DFMO. The combination of CsA (8.3 X 10(-4) mM) and alpha-DFMO (0.5 mM or 1.0 mM) inhibited H2T cell survival to a greater extent than either agent alone. These results suggest that CsA in combination with other agents that inhibit polyamine synthesis may be useful for the treatment of pancreatic cancer.
D000818:Animals; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003524:Cyclosporins / Q000008:administration & dosage*; D004357:Drug Synergism; D000518:Eflornithine / Q000008:administration & dosage*; D065108:Ornithine Decarboxylase Inhibitors; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000494:pharmacology
D003524:Cyclosporins; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011700:Putrescine; D000518:Eflornithine