title: Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth.
abstract: The effect of histamine and cimetidine on the growth of four human colon cancer cell lines was studied. Histamine significantly stimulated the uptake of tritiated thymidine in vitro in a dose dependent manner, to a maximum of 120% and 116% of controls for C170 and LIM2412, respectively. This effect was antagonised by cimetidine, but not diphenhydramine. Histamine also stimulated a dose dependent increase in cyclic adenosine monophosphate accumulation in C170 cells, antagonised by cimetidine. When grown as subcutaneous xenografts in Balb/c nu/nu mice, cimetidine had a significant inhibitory effect on the same two cell lines. The final volume of C170 tumours in animals given cimetidine was 44% of controls. This response was dose dependent, plateauing at a cimetidine dose of 50 mg/kg/day. The final volume of LIM2412 tumours in animals given cimetidine was 60% of controls. Histamine administered locally by a mini-osmotic pump stimulated C170 tumour growth to 164% of controls, was antagonised by cimetidine at a dose of 200 mg/kg/day, but not by lower concentrations. Histamine has a trophic effect on at least two colorectal cancer cell lines in vivo and in vitro. As this effect is antagonised by cimetidine, it may be mediated via tumour histamine type 2 receptors.
authors: University of New South Wales, Department of Surgery, St George Hospital, Kogarah, NSW, Australia.
authors: W J
authors: WJ
authors: Adams
authors: J A
authors: JA
authors: Lawson
authors: D L
authors: DL
authors: Morris
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D000242:Cyclic AMP / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011897:Random Allocation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP