論文名稱:

檳榔子水萃取物在人類口腔細胞中對E-cadherin的調控

 

The Regulation of E-cadherin in Human Oral Cells by Areca Nut Extract

研究生:

曾羽辛  Yu-Hsin Tseng

 

(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:

林姝君  Shu-Chun Lin

        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:

38917007

          學年度:

90

          語文別:

中文

 

英文

          出版年:

91

關鍵字:

檳榔子水萃取物  areca nut extract

 

口腔癌細胞株  oral squamous cell carcinoma cell line,OECM-1

 

正常人類口腔角質細胞培養  normal human oral keratinocyte,NHOK

全文說明:

電子全文

摘要:

中文摘要 口腔癌在台灣男性癌症中排名第五位,且有日漸嚴重的趨勢,經流行病學統計顯示,台灣80﹪的口腔癌病患有嚼食檳榔的習慣3,雖然尚未證實檳榔會直接誘使口腔癌的形成,但嚼食檳榔確實會增加口腔癌之罹患率,所以在本實驗中,利用檳榔子水萃取物(Areca nut extractANE)處理口腔細胞,觀察口腔細胞的外觀及蛋白質分子變化,藉而推測檳榔對口腔癌的影響。

 

在實驗中發現ANE會造成口腔癌細胞株(oral squamous cell carcinoma cell lineOECM-1)和正常人類口腔角質細胞培養(normal human oral keratinocyte,簡稱NHOK)的細胞型態發生明顯改變,細胞骨架有重新排列的情形,在OECM-1方面,以ANE處理過後,細胞間隙變大,造成細胞鼓起,且細胞間都有明顯F-actin組成的束狀構造產生,而在NHOK方面,細胞有明顯拉長的情況。由於細胞型態的改變與細胞貼附能力有極大的相關性,而上皮細胞中最主要的附著因子為E-cadherin,通常E-cadherin存在時,細胞會正常貼附,一旦功能缺損可能導致侵襲或轉移,亦即產生惡性瘤(carcinoma)最重要之表現型之一,且過去的研究指出鱗狀上皮細胞癌通常會缺乏E-cadherin的表現,或者會有功能喪失的情況,所以進一步探討ANE是否會調控E-cadherin,結果發現ANE會造成OECM-1中之E-cadherin的貼附功能下降,而NHOK中的E-cadherin表現量也受到抑制。為了更進一步知道ANE是否會造成OECM-1的移動能力上升,利用倒立顯微鏡在固定視野下進行連續攝影,發現ANE並未促進細胞的移動。過去的研究指出,E-cadherin可能受Rac-1Src的調控,ANE處理OECM-1後,Rac-1的表現量並未受到明顯的調控,而Src下游的β-catenin會受ANE誘發,而表現略增,未來可由這些與E-cadherin相關的分子,繼續探討檳榔導致口腔癌的可能路徑。

   
 

Abstract Oral squamous cell carcinoma (OSCC) is the fifth leading cancer in the male population in Taiwan. Areca chewing is strongly associated with the high incidence of oral cancer in Taiwan. In this study, I treated an OSCC cell line, OECM-1 and normal human oral keratinocytes (NHOK) with areca nut extract (ANE), to observe the molecular changes in oral cells, and to link the association between oral cancer formation and Areca chewing. ANE induced the morphological changes of oral cells. It caused a process formation interconnecting with neighboring OECM-1 as well as the separation of cells. It also caused the re-organization of stress fiber in NHOK. It was known that cell morphology is strongly associated with cell adhesion and E-cadherin is the key adhesion molecule in epithelial cell. The loss of E-cadherin may elicit signals to induce invasion and metastasis, a characteristic phenotype of malignancy. Previous findings have also showed that E-cadherin function can be abrogated in the process of cacinogenesis. So our experiment was targeted to the change of E-cadherin modulated by ANE. The results showed a remarkable relocation of E-cadherin in OECM-1 and NHOK through the treatment of ANE. However, no effect in ANE in mediating OECM-1 mobility was observed. E-cadherin may be regulated by Rac-1 or Src signaling cascade. This study has demonstrated that Rac-1 expression was not induced by ANE, however, the expression of β-catenin, a downstream effecter of Src, expression was up-regulated by ANE in OECM-1. Therefore, the complicated association between of E-cadherin and Rac-1 or Src pathways in oral cells as modulated by ANE should be further investigated.