title: Effects of cyclosporin A and alpha-difluoromethylornithine on the growth of hamster pancreatic cancer in vitro.
abstract: 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.
mesh_terms: 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
chemical_list: D003524:Cyclosporins; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D011700:Putrescine; D000518:Eflornithine