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標題: 高度醣化終產物活化RAGE對大腸癌化之促進效應與介入天然酚類化合物之影響
Age-induced RAGE Activation in Colorectal Tumorigenesis and the Effect of Natural Phenolics Intervation
作者: 顏國欽
關鍵字: 基礎研究;Advanced glycation end products (AGEs);食品科技;高度醣化終產物 (AGEs);高度醣化終產物受器 (RAGE);大腸癌化;天然酚類化合物;飲食型態;發炎;receptor for AGEs (RAGE);naturalphenolics;colon carcinogenesis;dietary style;inflammation
97 年度衛生署統計資料顯示,國內大腸癌病例逐年增加,經流行病學調查結果後發現,大腸癌罹患率的增加與國人飲食習慣的改變可能具有相關性。飲食型態轉變,導致國人攝入大腸刺激物的機會增加,由於大腸受到刺激會產生慢性發炎,因此,提高了大腸癌化 (colorectal tumorigenesis) 的機會。廣泛存在於加工食品中之梅納反應產物—高度醣化終產物 (advanced glycationend products, AGEs) 為一種醣毒性物質 (glycotoxin),其具有促發炎性質且不易被人體吸收代謝;然而,已有文獻證實,大腸細胞癌化程度與其膜上AGEs 特異性受器(receptor for AGEs, RAGE) 之活化程度具有顯著正相關性,故AGEs 極有可能經活化腸壁細胞上之RAGE 而刺激大腸發炎與促進大腸癌化。由於AGEs 可能為食物中的大腸刺激物之一,故探討AGEs-RAGE 作用對大腸癌化之影響是非常有意義的研究。基於此部分文獻目前仍鮮少資料可尋,因此本計畫擬針對此問題進行探討。大腸癌的發生與飲食息息相關,因此利用飲食來預防大腸癌無非是一最佳的防癌策略。多年來,本研究室致力於研究天然食品中具有化學預防作用的成分,發現天然抗氧化成分如酚酸、類黃酮等具有防癌的潛力,因此,本計畫以先前研究成果發現之具有防癌潛力的天然酚類化合物為對象,探討其對於AGEs-RAGE 作用相關之大腸癌化的影響。綜合上述,本研究計畫將分三年進行探討食品中AGEs 活化RAGE 對大腸癌化之促進效應與介入天然酚類化合物之影響:第一年度以人類大腸癌細胞為模式,探討AGEs 刺激RAGE 對大腸癌細胞生長及侵入轉移能力之影響及其與RAGE 表現的相關性。第二年度則以動物試驗探討AGEs 刺激RAGE 活化對於大腸癌化之促進效應。第三年度計畫以人類大腸癌細胞為模式,評估天然酚類化合物抑制大腸癌化之潛力,並探討AGEs-RAGE 作用與大腸癌化相關調控因子表現之關聯性,以及介入天然酚類化合物後的影響。本為期三年之計畫將可以清楚了解AGE-RAGE 作用對大腸癌化促進之影響,並可得知天然酚類化合物抑制與AGEs-RAGE 作用相關之大腸癌化的功效,研究成果極具預防大腸癌之參考價值。

The latest statistics show that patients with colon cancer in Taiwan are increasing everyyear. It is probably associated with alteration of dietary style. People now eat moreanimal food which contain amounts of toxin, so the risk of colon inflammation andmoreover carcinogenesis become higher. Advanced glycation end products (AGEs) are avariety of glycotoxins in food, produced in the course of food-processing and cooking.Because dietary AGEs are difficult to be metabolized, they are likely to accumulate in thebody. Many studies indicate that AGEs can activate the receptor for AGEs (RAGE) oncell membrance then contributing to inflammatory response in the body. Owing to themain function of colon is to absorb water and storage the dregs of food, colon endothelialcell may get AGE-induced damage. RAGE is a membrance-associated receptor, whichhas multiple extracellular ligands. Recent years, there are a group of discussions aboutRAGE activation implicating in the pathogenesis of various inflammatory disordersincluding cancer. Ligation by RAGE may activate a series of signal-modulatingmolecule in cancer cell and generate proliferation, invasion and metastasis of cancer cells.Also, researches indicate that activation of RAGE is closely related to coloncarcinogenesis. Because AGEs are specific ligands of RAGE, we try to evaluate whetherAGEs can promote colon carcinogenesis by engagement of RAGE. The project will bedivided into three parts to be performed in three years. In the first year's plan, the invitro model system will be used to treat the effect of AGE-RAGE ligation on theproliferation, invasion and metastasis of colon cancer cells. In the second year's plan, theanimal model system will be used to evaluate the promoting effect of AGE-RAGE ligationon colon tumorigenesis. For the past two decades, the cancer preventive abilities ofnatural antioxidant have been reported wildly in many studies. Our previous studies alsoshowed that phenolics have good anti-cancer property. Therefore, in the third year's plan,we will assess the effect of natural phenolics on AGE-RAGE ligation promoting coloncarcinogenesis and elucidate the molecular mechanism. In this three year's project, thepromoting effect of AGE-RAGE ligation and the inhibitory effets of natural phenolics oncolon carcinogenesis will be clarified. The results of this study will provide additionalstrategy for prevention of colon cancer.
其他識別: NSC99-2628-B005-002-MY3
Appears in Collections:食品暨應用生物科技學系

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