Suppression by apigenin of peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats

The effect of a naturally occurring flavonoid apigenin on the development o f bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas i nduced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 mug /kg body weight) every other day, and from week 16, s.c. injections of apig enin (0.75 or 1.5 mg/kg body weight) every other day until the end of the e xperiment in week 45. Bombesin significantly increased the incidence of int estinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no ef fect on the enhancement of intestinal carcinogenesis by bombesin, the locat ion, histologic type, depth of involvement, infiltrating growth patterns an d labeling index, it was found to decrease significantly the incidence of c ancer metastasis. Apigenin significantly decreased the incidence of lymphat ic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In v itro experiments revealed that apigenin inhibited bombesin-enhanced phospho rylation of mitogen-activated protein kinase (MAPK), but not matrix metallo protease (MMP)-9 expression. Our findings indicate that apigenin inhibits c ancer metastasis through inhibition of phosphorylation of MAPK.