| Summary: | 碩士 === 國立陽明大學 === 口腔生物研究所 === 94 === Abstract：
In the biological process of development, tissue remodeling, wound healing and process of carcinogenesis, fractions of epithelial cell might loss their original characteristics transiently or permanently. Furthermore, fibroblastoid mesenchymal cellular phenotypes may appear from these cells. For instance, cell may transfer from original epitheloid shape to spindle shape; and loss of cell adhesion and appearing of connective tissue cytoskeleton,vimentin, may occur. The production of protease may also be induced to degrade basement membrane that is advantageous for invasion. Such transition was considered a de-differentiation, a trans-differentiation or an epithelial-mesenchymal transition (EMT). Areca chewing is highly associated with oral carcinogenesis. This study addresses the implication of areca nut extract (ANE) in oral carcinogenesis. Previous studies in our laboratory have shown that ANE treatment can induce EMT-like changes in OECM-1 and OC3 oral cancer cells. The changes included (1) the transfer of cell to spindle shape (2) induction of vimentin expression and (3) internalization of E-cadherin. Because ANE can elicit multiple signaling pathways, this study explored if ANE-induced PI3K/AKT activation is responsible for EMT-like phenotypes. It was found that the pretreatment with PI3K inhibitors Worthmannin and LY294002, the phosphorylation of AKT and GSK, up-regulate vimention and the internalization of E-cadherin can be abrogated. The findings suggested the involvement of AKT and GSK in the genesis of these EMT-like phenotypes. Since such pretreatment was unable to revert the spindle morphological shape induced by ANE, pathways other than PI3K could be involved in the induction of EMT-like changes modulated by ANE. Further dissection of other pathways will elucidate mechanisms involved in oral pathogenesis as induced by ANE.
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