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標題: | Sirtuin 5經由阻斷27-羥基膽固醇生成以抑制口腔鱗狀細胞癌之研究 A study on suppression of oral squamous cell carcinoma by sirtuin 5 through its inhibition of 27-hydroxycholesterol production |
作者: | Fang-Yu Wu 吳芳育 |
指導教授: | 郭生興 |
關鍵字: | 口腔鱗狀上皮細癌,27-羥基膽固醇,棕梠酸,sirtuin 5,上皮間質轉化, Oral squamous cell carcinoma,27-hydroxycholesterol,palmitic acid,sirtuin 5,epithelial-mesenchymal-transition, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 細胞代謝已被證實與多種癌症有關,其中肥胖及膽固醇的代謝也被發現與癌症有關,然而膽固醇代謝與口腔癌之間的關係在過往文獻中並不清楚。
過往文獻顯示,在膽固醇排出影響口腔癌生長、或是不同癌症的轉移,皆可與膽固醇的代謝產物27-羥基膽固醇相關,27-羥基膽固醇是否能影響口腔癌,是我們關注的重點。而棕梠酸被證實能開啟口腔癌細胞的轉移,其與27-羥基膽固醇之間的關係,也是我們研究的方向。 本研究主要分成三大部分:第一部分是研究27-羥基膽固醇促進口腔癌細胞的機轉,包含27-羥基膽固醇能促使口腔癌細胞表現上皮間質轉化及促進口腔癌細胞遷移能力,第二部分研究棕梠酸能促進口腔癌細胞生成27-羥基膽固醇及上皮間質轉化,第三部分則為研究SIRT5抑制上述機轉達到抑制口腔鱗狀上皮細胞癌之效果。 我們第一部分結果顯示27-羥基膽固醇能促進口腔癌細胞表現上皮間質轉化並能促進其遷移、侵入的能力,並且有時間跟濃度上的相關性。第二部分我們發現棕梠酸能增加口腔癌細胞表現膽固醇27-羥化酶,有時間與濃度的相關性,並可增加口腔癌細胞27-羥基膽固醇生成量,及促進上皮間質轉化。第三部分我們發現將口腔癌細胞過度表現SIRT5時,其膽固醇27-羥化酶表現會下降,上皮間質轉化會被抑制且遷移能力會下降。 這些實驗結果相當鼓舞我們的研究方向,我們認為SIRT5與膽固醇代謝對於治療或抑制口腔鱗狀細胞癌轉移具有相當程度的潛力,其中機制非常值得進一步研究與探討。 Cell metabolisms had been proved to have relation with many cancers. Obesity and cholesterol metabolism had been found linked to cancer. However, the relation between cholesterol metabolism and oral cancer was not clear in the literatures. A key word among the results of studies from cholesterol efflux influencing growth of oral cancer cell and many cancer metastasis was 27-hydroxycholestrol. We focused on the influence of 27-hydroxycholestrol to oral cancer cells. Palmitic acid had been proved that it can initiating the metastasis of oral cancer cells. The relation between 27-hydroxycholestrol and palmitic acid was also a topic which we were interested. This study can be divided into three part. The first was research on 27-hydroxycholestrol promoting epithelial-mesenchymal-transition (EMT) and migration. The second part was palmitic acid can promote the oral cancer cell 27-hydroxycholestrol production and EMT. The third part was SIRT5 can suppressed oral squamous cell carcinoma through its inhibition of the mechanism we mentioned before. Our first part result showed 27-hydroxycholestrol can enhance oral cancer cell EMT and the migration, invasion ability, and it had dose and time effect. The second part was found that palmitic acid can enhance cholesterol 27-hydroxylase expression and stimulate oral cancer cell to increase the production of 27-hydroxycholestrol, and it had dose and time effect. The third part we found when we over-expressed SIRT5 in oral cancer cell, the expression of cholesterol 27-hydroxylase, EMT and migration ability will be lowered. These outcomes inspired our team, and we believed that the mechanisms of SIRT5 and metabolism of cholesterol had the promising potential for treating oral cancer or suppressing metastasis of oral cancer. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/70395 |
DOI: | 10.6342/NTU201802981 |
全文授權: | 有償授權 |
顯示於系所單位: | 臨床牙醫學研究所 |
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