論文名稱:

檳榔子水萃取物透過活化PI3K/Akt途徑誘發口腔癌細胞株呈現類似EMT相關變化之研究

 

Areca nut extract induces EMT-related phenotypes by activating PI3K/Akt signaling in oral cancer cells

研究生:

林淑慧  Shu-Hui Lin

 

(以作者名查詢陽明大學館藏系統)

 

(以作者名查詢全國圖書書目資訊網)

指導教授:

張國威  Kuo-Wei Chang

        學位類別:

碩士

        學校名稱:

國立陽明大學

系所名稱:

口腔生物研究所

            學號:

39317008

          學年度:

94

          語文別:

中文

          出版年:

95

關鍵字:

檳榔子水萃取物  ANE

 

上皮細胞轉形成間葉細胞  EMT

 

口腔癌  Akt

 

  E-cadherin

 

  vimentin

全文說明:

(本論文未授權公開)

 

電子全文

        論文頁數:

78

摘要:

中文摘要:

 

在正常發育過程、組織重組、傷口癒合和癌化過程中,部份上皮細胞會短暫或永久喪失原有的特徵,進而出現類似纖維母細胞相關型態及特徵,例如:(1)細胞由原本的上皮細胞型態轉變成類似結締組織的梭狀型態。(2)喪失上皮細胞間附著因子的功能。(3)表現結締細胞特有的細胞骨架蛋白vimentin。(4)分泌蛋白水解酶而破壞基底膜,進而侵襲結締組織。此過程被認為是細胞進行轉型、去分化或是上皮細胞轉形成間葉細胞(epithelial-mesenchymal transition,簡稱EMT)。嚼食檳榔者與口腔癌的關係密切,故本研究探討檳榔子水萃取物(ANE)在口腔癌症形成或進行中所扮演的角色。先前實驗室研究結果顯示,ANE處理OECM-1OC-3細胞,會誘發EMT相關型態出現,包括:(1)細胞出現梭狀型態。(2vimentin大量表現。(3E-cadherin由膜位移質內。由於ANE會誘發多種訊息傳導系統活化。故本研究探討ANE是否活化PI3K/Akt進而誘發這些EMT相關之型態,研究發現:使用PI3K抑制劑WortmanninLY294002可以抑制由ANE誘導活化的AktGSKvimentin下降和E-cadherin內移的現象,顯示ANE可透過PI3K活化AktGSK,但此抑制劑,並不能完全回復EMT的型態,顯示ANE可能部份透過PI3K參與類似EMT相關表型的進行,但並非完全由PI3K所調控的,可能有其他的機轉參與調控,值得深入研究。

 

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.