沒食子酸抑制小鼠腸癌轉移之作用

Gallic acid inhibits the metastasis of colon cancer cells in mice

陳昱宏(Yu-Hong Chen)

指導教授 ： 王朝鐘

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2015年)

摘要

大腸癌是佔所有因癌症死亡原因的第三位，與其他癌症相比較如肺癌，大腸和結腸癌透過定期篩檢是可以預防的。若早期發現有大腸癌，治癒率可高達 90％。因此如何治療大腸癌及探討大腸癌可能致病原因，是目前臨床上重要的研究方向。現今大腸癌的治療以手術切除為主，化學治療為輔，但癌症後期存活率偏低及手術後腸癌細胞易轉移，合併傳統化學藥物治療有嚴重的副作用等，使得病患治癒率低與復發率高。因此，開發新型藥物來輔助治療、延緩或抑制癌症發展是必需的。
天然物抗癌的研究是最近的潮流，而沒食子酸(GA)為天然具抗氧化能力的多酚類，可在五倍子、漆樹、金縷梅、茶葉、橡樹皮等植物中發現，且被證實對癌細胞有毒性反應，但並不會傷害健康細胞。首先我們進行MTT assay，使用DLD-1腸癌細胞株加GA、3-OMGA、4-OMGA處理，觀察DLD-1細胞的存活率，發現三種藥都沒有明顯的細胞毒性，所以接著進行DLD-1細胞傷口癒合實驗，我們發現隨著時間越久，GA這組細胞爬行的能力愈來越弱；接著在細胞轉移的實驗中，可以從transwell assay的結果觀察到，GA抑制細胞轉移的能力也是效果最好的；為了釐清其分子機制，我們藉由細胞骨架蛋白Src signal pathway的抑制路徑證實，GA經由調節CD44的訊息路徑有效的抑制DLD-1腸癌細胞的轉移作用，最後在動物實驗也證實，GA確實能抑制腸癌細胞DLD-1轉移能力。根據本篇的結果GA具有抗腸癌轉移的療效，未來可應用於化學預防上成為發展新藥。

關鍵字

沒食子酸

並列摘要

The colon cancer is cancer mortality rate death third, compare with other cancers as lung cancer, the large intestine and the colon cancer sieves examines is may prevent. If early discover colon cancer , the cure rate may reach as high as 90%.therefore how to cure the colon cancer and the discussion colon cancer cancer-causing possible, is clinical important research direction. The treatment of colon cancer operation excision as principle, chemistry treatment for assist, but cancer later period the survival rate low and after operation the cell easy to transfer, Merge traditional chemistry medicine treatment has serious side effect etc., make patient's cure rate is low and relapse high. Therefore, the development a new medicine assists the treatment, the postponement or the suppression cancer development is essential.
The natural anti-cancer research is the recent tidal current, gallic acid (GA) is the natural anti-oxidation ability phenolic compounds, can find in galla chinensis, lacquer tree, hamamelis , tea, ficus elastica discover...etc, be confirmed the toxicity responds poisonous to the cancer cell, but will not hurt the healthy cell. We conducted MTT assay, using the DLD-1 cancer of the intestines cell line to treated with different doses of GA, 3-OMGA, the 4-OMGA, observations DLD-1 cell viability, discovered three medicines do not have the obvious cell toxicity, then carries on the DLD-1 cell wound healing assay, we found that the long time, GA cells crawling ability weaker; Then in the metastasis experiment, observe from the transwell assay result, GA suppression cell transfer ability also is the effect best; In order to clarify its numerator mechanism, we analysis cytoskeletal proteins, adhesion molecules, and the specificity of inhibition of Src signal pathway to confirmed, GA via regulating CD44 signaling pathway effectively inhibited DLD-1 colon cancer cell metastasis effect. Finally also confirmed at the animal experimentation that, GA can inhibited cancer cell DLD-1 metastasis ability. According to this result GA has anti-colon cancer of the metastasis ability, future might apply in chemistry prevention becomes develops the new medicine.

並列關鍵字

Gallic acid

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