Chemoprevention of chemically-induced intestinal carcinoma in rats by combined octreotide, galanin and serotonin treatment and by cyclooxygenese-2 inhibitor

ME El-Salhy, PhD, MD

Public Health and clinical Medicine, Umeå, V�sterbotten Sweden

AIM: To establish whether triple treatment with octreotide, galanin and serotonin as well as COX-2 inhibitor, at the time of exposure to a carcinogen has a chemopreventive effect against intestinal cancer. METHODS: Three groups of 20 rats each were injected s.c. once a week, for 12 weeks, with 21 mg/kg body weight with 1,2 dimethylhydrazine dihydrochloride. On the same day of carcinogen injection, the first group received a s.c. injection of a mixture of 10 microg of octreotide, galanin and serotonin/kg body weight. The second group received 2 mg/kg body weight Coxiberin p.o. The animals were left for another 13 weeks without any treatment. The rats were then killed and inspected for possible tumours. The tumours were noted for their location, number and size, and were removed for histopathological identification. RESULTS: The incidence of small intestinal tumours was significantly lower in the animal groups treated with regulatory peptides/amine and with COX-2 inhibitor than in controls. The incidence, the volume and metastatic potentials of colon carcinoma were significantly lower in the group of rats that received COX-2 inhibitor than in controls. There was no significant difference between the group of rats treated with the regulatory peptides/amine and controls regarding the incidence of colon tumours, tumour volume, or metastasis. CONCLUSION: Triple treatment with octreotide, galanin and serotonin has a preventive effect against small, but not against large intestinal cancer. Treatment with COX-2 inhibitor has a preventive effect against both small and large intestinal cancer.

KEY WORDS: carcinoma, chemoprevention, colon, Cox-2.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.