A total of 40 areca quid chewing-associated OSCCs and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, extracellular signal-regulated protein kinase inhibitor PD98059, glutathione precursor N-acetyl-l-cysteine (NAC), tyrosine kinase inhibitor herbimycin-A, p38 inhibitor SB203580, and phosphatidylinositaol 3-kinase inhibitor LY294002 were added to find the possible regulatory mechanisms.
¦Â-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p?<?0.05). It was demonstrated that normal oral epithelium showed only membranous staining for ¦Â-catenin, and membranous staining was lost or reduced with an increase in cytoplasmic/nuclear staining in OSCCs. Arecoline was found to elevate ¦Â-catenin expression in a dose-dependent manner (p?<?0.05). The addition of PD98059, NAC, herbimycin-A, SB203580, and LY294002 markedly inhibited the arecoline-induced ¦Â-catenin expression (p?<?0.05).
¦Â-catenin expression is significantly upregulated in areca quid chewing-associated OSCC. The localization of ¦Â-catenin expression is correlated with the tumor size and clinical stage. In addition, ¦Â-catenin expression induced by arecoline is downregulated by PD98059, NAC, herbimycin-A, SB203580, and LY294002.