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研究生:陳柏任
研究生(外文):Chen Po-Jen
論文名稱:檳榔子萃取物抑制CHES1負調控於口腔癌細胞生長之作用
論文名稱(外文):Areca nut inhibit CHES1 negative regulation on the growth of oral cancer cells
指導教授:鄭恩加
指導教授(外文):Cheng ann-joy
學位類別:碩士
校院名稱:長庚大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:英文
論文頁數:60
中文關鍵詞:檳榔子口腔癌細胞生長
外文關鍵詞:areca nutCHES1oral cancer
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口腔癌是台灣第六大的癌症,而且台灣口腔癌的特徵和其他亞洲或西方國家有很大的不同,這可能是因為致癌因子的使用習慣和基因表現不同所造成的。而在台灣有85 %的口腔癌患者有嚼食檳榔的習慣,檳榔也已經被證實是口腔癌主要的致癌因子,然而其中的分子機制仍然不清楚。在本研究中,我們發現經過檳榔子萃取物中含量最豐富的成分arecoline處理三天之後,arecoline可以抑制口腔癌細胞的生長,並且在更高濃度的處理之下造成細胞毒性。Arecoline造成的生長抑制伴隨著細胞週期的停止,使細胞週期停留在S或G2/M時期。此外,經過arecoline三天的處理之後,arecoline可以抑制CHES1 mRNA的表現,並且在5-30分鐘的處理之下誘導ERK1/2的磷酸化,並且抑制ERK1/2的活化可以稍微回復arecoline所抑制的CHES1表現。另一方面,CHES1的大量表現可以抑制20-50 %細胞的生長和細胞群落的形成,使細胞週期停留在S和G2/M時期,並且可以降低arecoline所引起的細胞毒性,因此我們推測CHES1可能在口腔癌細胞中扮演一個腫瘤抑制的功能。Arecoline可能經由活化ERK訊號傳遞路徑來抑制CHES1的表現,進而抑制其對於口腔癌細胞生長的負調控,而這個機制可能在檳榔所引起的口腔癌形成中,扮演了一個重要的角色。
Oral cancer is the 6th most frequent cancer in Taiwan. The instant rates of oral cancer in Western, Asian countries and Taiwan are different that maybe resulted from the distinct exposure of carcinogens and various in genetic predisposition. In Taiwan, approximately 85 % of all oral cancer patients are associated with betel quid (BQ) chewing which is the main etiological factor of oral cancer. Thus, the local molecular mechanisms deserve investigation. In this present study, we find that arecoline, the most abundant component of areca nut (AN) extract, was able to inhibit the growth of oral cancer cells at the concentrations 120-400 µM and render a cytotoxicity effect at higher doses dependent on OEC-M1, SCC-25 and KB cells. This growth inhibition is accompanied with the arrest of oral cancer cells in either S or G2/M phases after 3 days of arecoline treatment. Moreover, arecoline cause the suppression of CHES1 mRNA expression after 3 days of treatment, along with the induction of ERK1/2 phosphorylation at 5-30 min of exposure. However, inhibition of ERK1/2 activation can slightly restore the arecoline- inhibited CHES1 expression. In addition, CHES1 over- expression can inhibit cell growth and colony formation to about 20-50%, and cause cell cycle slightly arrest in S or G2/M phase, suggesting CHES1 negatively regulate cell growth. The arecoline-induced cytotoxicity also can be slightly reduced in CHES1 over-expressed SCC-25 cells. We, therefore, postulate that CHES1 may possess tumor suppressor functions. AN extract inhibit CHES1 negative regulation on the growth of oral cancer cells that may be regulated by ERK pathway. This mechanism may play a significant role in the BQ chewing-induced oral carcinogenesis.
Content
Page
指導教授推薦書
口試委員會審定書
授權書 iii
誌謝 iv
摘要 v
Abstract vi
Content vii
List of figures viii
Background 1
Rationale and specific aim 10
Methods and materials 11
Results 18
Discussion 25
References 32
Figures 44
Reference
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