新型查耳酮衍生化療藥物誘導人類口腔癌細胞凋亡機制的探討

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題名:	新型查耳酮衍生化療藥物誘導人類口腔癌細胞凋亡機制的探討 A novel chalcone analogue as a chemodrug promotes cell apoptosis of human oral cancer cells
作者:	張豈睿;Chang, Kai-Ruei
貢獻者:	基礎醫學研究所碩士班
關鍵詞:	口腔鱗狀癌細胞;細胞週期;癌細胞轉移;oral squamous carcinoma cells (OSCC);cell cycle;migration
日期:	2012-07-30
上傳時間:	2012-08-31 16:33:17 (UTC+8)
出版者:	中國醫藥大學
摘要:	口腔癌是目前世界上多數流行的癌症之一，在台灣其好發率占所有癌症第六位。如同其它癌症，傳統手術治療的效果並不如預期。因此，我們迫切需要開發一種新穎且能夠有效治療口腔癌症病患的方法。先前的研究證實一系列的查爾酮(chalcones)類似物在各種癌細胞型態具有抗腫瘤的活性。然而，卻沒有查爾酮治療口腔癌的相關報導。在本論文中，我們進一步研究3,3',4',5'-trimethoxychalcone (TMC)是否具有對抗口腔癌的生物活性。我們的研究結果顯示TMC能夠有效的抑制各種不同的口腔鱗狀癌細胞(oral squamous carcinoma cells, OSCC)，但對於正常細胞(人類口腔齒齦細胞株)並不會造成任何影響。TMC抑制口腔癌細胞的分子機制主要透過讓癌細胞靜止於細胞週期G2/M時期。TMC也會造成抗細胞凋亡蛋白Bcl-2的表現量隨著藥物劑量增加而減少；而伴隨細胞凋亡蛋白如Bax與Bak則是會隨著藥物劑量增加表現量上升。此外，在西方墨點法與癌細胞轉移試驗中顯示出CCL5能誘導口腔癌細胞轉移，並活化金屬蛋白蛋白酶-9 (metalloproteinase-9, MMP-9)。然而，這種影響能藉由TMC處理細胞後而加以抑制。我們的研究結果顯示，查爾酮類似物具有多方面發展的潛力，在其多功能的活性中不只具有對口腔癌細胞產生細胞毒殺，同樣的也能夠減緩口腔癌細胞轉移能力。 Oral cancer is one of the most prevalence cancers in the world and has became at the 6th leading cancer in Taiwan. Like many cancers, potent effects of surgical treatment are not as expected. Therefore, it is urgent to develop an effective treatment for curing oferadicating the oral cancer patients. A series of chalcone analogues have been found harboring anti-cancer activity in several cancer types. However, the report for treatment of oral cancer with chalcone was absent. In the present study, we assessed that whether 3,3',4',5'-trimethoxychalcone (TMC) has the biological activities in the inhibition of oral cancer. Our data showed that TMC is able to inhibit several oral squamous carcinoma cell lines, but has no effect on normal cells (oral fibroblast cells). The molecular mechanism of TMC in the inhibition of oral cancer cells was arrested cell cycle at G2/M phase. TMC caused a dose-dependent decrease in protein expression of anti-apoptotic protein Bcl-2, with concomitant increasing in pro-apoptotic protein Bax and Bak. Additionally, western blot and migration studies demonstrated that stimulation of oral cancer cells with CCL5 directly increased the migration and metalloproteinase-9 (MMP-9) production. However, this effect was attenuated by treatment of cells with TMC. The results from this study indicated that development of chalcone analogues might have multiple functions not only cytotoxic against oral cancer cells but attenuation of oral cancer cell migration.
顯示於類別:	[基礎醫學研究所] 博碩士論文

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