Suppression by verapamil of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats

Background: The effects of combined administration of bombesin and verapami l hydrochloride (verapamil), a calcium channel blocker, on the incidence of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethan e (AOM) and the labeling index of intestinal cancers were investigated in m ale Wistar rats. Methods: From the beginning of the experiment, rats were g iven 10 weekly subcutaneous injections of AOM (7.4 mg/kg body weight) and s ubcutaneous injections of bombesin (40 mug/kg body weight) every other day, and from week 16, intraperitoneal injections of verapamil (10 or 20 mg/kg body weight) every other day until the end fo the experiment in week 45. Re sults: Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum. Although verapamil administered at either dose had little or no effect on the enhancement of intestinal carci nogenesis by bombesin or on the location, histologic type, depth of involve ment, labeling index, apoptotic index or tumor vascularity of intestinal ca ncers, it significantly decreased the incidence of cancer metastasis. Verap amil also significantly decreased the incidence of lymphatic invasion of ad enocarcinomas, which was enhanced by bombesin. Conclusion: These findings i ndicate that verapamil inhibits cancer metastasis through actions that do n ot affect the growth of intestinal cancers. Copyright (C) 2001 S. Karger AG , Basel.