misoprostol and Adenocarcinoma

A synthetic prostaglandin E1 (PGE1) analogue, misoprostol, was investigated for its effects on the growth of colon cancer in two in vivo models. Human colon cancer cell lines C170, LIM2412 and LIM2405 were grown as subcutaneous xenografts on T-lymphocyte deficient ARC(s) nu/nu mice. Tumour volumes were found to be significantly inhibited compared with control in misoprostol-treated animals with two cell lines. C170 was inhibited by 70.5% (P = 0.0001) and LIM2412 by 68.2% (P = 0.01). LIM2405 was inhibited by 33% (P = 0.14) which was not significantly different from the control. In a second experiment, colon cancers were induced in Sprague-Dawley rats using 1,2 dimethyl-hydrazine (DMH). After 10 weeks of treatment, rats were randomized to receive a 5 week course of 20 micrograms/kg per day of oral misoprostol. Misoprostol-treated rats were found to have a similar tumour incidence and staging compared with control animals. Oral administration of misoprostol has an inhibitory effect on early tumour growth of some colonic cancers, but not on established tumours.

Topics: Adenocarcinoma; Analysis of Variance; Animals; Colonic Neoplasms; Dimethylhydrazines; Female; Humans; Mice; Mice, Nude; Misoprostol; Neoplasm Invasiveness; Random Allocation; Rats; Rats, Sprague-Dawley; Transplantation, Heterologous; Tumor Cells, Cultured

The purpose of this study was to investigate the effect of long-term misoprostol administration, at non-antisecretory doses, on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-induced gastric carcinogenesis. The incidence of gastric carcinomas and precancerous lesions was evaluated in 50 male 250-g Sprague-Dawley rats after 52 weeks of continuous oral administration of MNNG (120 mg/l; n = 20), MNNG plus misoprostol (2 mg kg-1 day-1; n = 20) or tap water (n = 10) (experiment 1), and in 30 rats treated with MNNG for 30 weeks followed by tap water (n = 15) or by misoprostol (n = 15) for 22 weeks; a third group (n = 10) received tap water only for 52 weeks (experiment 2). After sacrifice, gastric mucosal lesions were macroscopically evaluated and their histology obtained. MNNG consumption was comparable in all groups (6.5 +/- 1.1 mg rat-1 day-1). Misoprostol consumption was 180 +/- 0.25 mg kg-1 day-1 rat-1. In experiment 1 the incidence of gastric carcinomas was 60% in the MNNG group and 25% in the group treated with MNNG plus misoprostol (P less than 0.05). Cytotoxic and hyperplastic gastric mucosal lesions were also significantly reduced by misoprostol. In experiment 2 the incidence of carcinomas was 31% and 38.6% respectively. Misoprostol significantly decreased the incidence of gastric cancer formation when given from the beginning of the experiment. By contrast, when administered after 30 weeks of MNNG treatment it did not interfere with experimental gastric cancer formation. Exogenous prostaglandins are able to prevent the early MNNG-induced gastric mucosal lesions, thus interfering with gastric carcinogenesis.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Cell Nucleus; Cystadenocarcinoma; Male; Methylnitronitrosoguanidine; Misoprostol; Rats; Rats, Inbred Strains; Stomach Neoplasms; Time Factors