Antimetastatic effect of cimetidine on mice bearing a C3H mouse mammary adenocarcinoma: survival and lymphocyte function studies.
It has been reported that treatment with cimetidine, a histamine H2-receptor antagonist, increased survival and decreased the number of lung metastases in mice bearing the Lewis Lung carcinoma [29]. It was suggested that this effect was due to the ability of cimetidine to block histamine activation of suppressor lymphocytes and hence allow host defence mechanisms to inhibit tumour growth. In the present studies, C3H/He mice were implanted with a C3H mouse mammary adenocarcinoma on Day 0. This tumour metastasizes to the lungs in 30-50 days. Primary tumours were ablated with X-rays when they had grown to about 0.2 g and animals were given drinking water with or without cimetidine (10 mg ml-1) until the end of the experiment. Cimetidine reduced the number of mice dying from metastatic disease from 7/15 (controls) to 3/13. Cimetidine treatment also prolonged survival of mice that did succumb to metastatic disease by about 12 days. The response of spleen lymphocytes to the mitogens phytohaemagglutinin and lipopolysaccharide was assessed in vitro by uptake of 3H-thymidine 0, 16, 45 and 58 days after tumour implantation. Lymphocyte responsiveness was depressed by tumour burden. The influence of cimetidine treatment was equivocal being dependent upon time after tumour implantation and dose of mitogen. In this mouse-tumour system, the mechanism of the antimetastic effect of cimetidine is different from that previously suggested [29].
D000818:Animals; D002478:Cells, Cultured; D002927:Cimetidine / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006632:Histamine / Q000494:pharmacology; D007108:Immune Tolerance; D008175:Lung Neoplasms / Q000556:secondary; D008213:Lymphocyte Activation / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis / Q000188:drug therapy*
D002927:Cimetidine; D006632:Histamine