Green tea selectively targets initial stages of intestinal carcinogenesis in the AOM-ApcMin mouse model

摘要

One of the liabilities of the ApcMin mouse as a model for colon cancer is its lack of a robust tumor response in the large bowel. In our protocol, we treated the ApcMin mouse with azoxymethane, a colon-selective carcinogen. This protocol induced a 4-fold increase in the number of colon tumors. We utilized this protocol to investigate the possible mechanisms of inhibition of colorectal carcinogenesis by green tea. Mice received water or a 0.6% (w/v) solution of green tea as the only source of beverage. Green tea treatment commenced at the eighth week of age and lasted for either 4 or 8 weeks. Green tea significantly inhibited the formation of new adenomas, but was ineffective against larger tumors. Mechanistically, we investigated the effects of green tea on the expression of biomarkers involved in colon carcinogenesis. Western blotting analysis showed that green tea decreased the total levels of the early carcinogenesis biomarker β-catenin and its downstream target cyclin D1. In contrast, the expression of COX-2 was not altered. Immunohistochemical analysis showed that green tea inhibited the formation of adenomas overexpressing β-catenin and cyclin D1, but did not reduce the number of COX-2-expressing adenomas. Our results suggest that green tea specifically targets initial stages of colon carcinogenesis; the time of administration of green tea is pivotal for effective chemoprevention. Beverage levels of green tea do not inhibit the progress of any large adenomas or adenocarcinomas existing prior to the tea administration.