Effects of cyclosporine and alpha-difluoromethylornithine on the growth of mouse colon cancer in vitro.
The growth and survival of mouse (MC-26) colon carcinoma in vitro and in vivo are significantly reduced by inhibitors of polyamine biosynthesis. alpha-Difluoromethylornithine (DFMO), is a specific and irreversible inhibitor of ornithine decarboxylase (ODC); the rate-limiting enzyme in polyamine biosynthesis. DFMO treatment inhibits the growth of MC-26 colon cancer cells and decreases MC-26 cell survival both in vitro and in vivo. In the present study, we examined the effects of cyclosporine (CsA) on growth, survival, and polyamine levels in MC-26 colon cancer in vitro. CsA had inhibitory effects on MC-26 colon cancer growth which were similar to DFMO; these effects were blocked by the addition of the polyamine, putrescine. The combination of CsA (8.3 X 10(-4) mM) and DFMO (0.5 mM or 1.0 mM) inhibited MC-26 cell survival to a greater extent than either agent alone. These results suggest that CsA given in combination with other agents which inhibit polyamine synthesis may be useful for the treatment of colon cancer.
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003524:Cyclosporins / Q000494:pharmacology*; D000518:Eflornithine / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D011073:Polyamines / Q000378:metabolism*
D003524:Cyclosporins; D011073:Polyamines; D000518:Eflornithine