We previously showed that colitis enhanced the development of cancer and aberrant crypt foci (ACF) in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in Fischer 344 rats. In this study, we examined the effect of two different anti-inflammatory drugs [non-steroidal anti-inflammatory drugs (NSAIDs: Fenbufen) and a platelet activating factor-receptor antagonist (PAF-RA)] on the inflammation-induced rat colon carcinogenesis. Furthermore, we examined the expression and the localization of β-catenin protein, and the proliferating cell nuclear antigen (PCNA)-labeling index (LI) in ACF and cancer. PAF-RA significantly decreased the incidence of ACF in the rats (p<0.05), but Fenbufen did not affect the incidence of ACF and cancer. In most of the ACF (91%), β-catenin was localized at the cell membrane like in normal colon epithelium. In about 9% of the ACF, β-catenin was overexpressed not only on the cell membrane but also in the cytoplasm. In all of the cancer cells, β-catenin was overexpressed in the nucleus. When we compared the PCNA-LI in the ACF showing normal β-catenin expression pattern with that in the ACF showing abnormal β-catenin expression pattern (overexpression in cytoplasm), there was no significant difference of the PCNA-LI in these two different types of ACF. These findings suggest that immunohistochemical staining of ACF for β-catenin can evaluate the malignant potential of ACF, and that PAF-RA can be used for preventing the development of ACF in inflammation-induced carcinogenesis.

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