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標題: | Egr-1 於大腸癌幹細胞之功能研究 The Role of Egr-1 in Colorectal Stem Cells |
作者: | You-Chun Lin 林宥君 |
指導教授: | 陳彥榮 |
關鍵字: | 大腸癌,癌幹細胞,Egr-1,常山萃取物,分化, colorectal cancer,cancer stem cell,Egr-1,Dichroa febrifuga extract,differentiation, |
出版年 : | 2018 |
學位: | 碩士 |
摘要: | 癌幹細胞具有較強的抗化療藥物以及轉移能力,因此不易治療根除,被認為是導致癌症復發及轉移的原因。Egr-1 為轉錄因子可以調控細胞的增生及凋亡,也會促使幹細胞的分化。而在癌症的研究中發現 Egr-1 同時作為促癌基因和抑癌基因,但是目前還不清楚 Egr-1 對於癌幹細胞的影響。本篇研究在大腸癌細胞株 DLD1 中過量表現及削弱 Egr-1,並藉由球體及群落形成檢測、群落抗藥性試驗、邊緣族群分析、大腸癌幹細胞標記表現量檢測以及轉移能力分析,發現 Egr-1 會透過抑制癌幹細胞的自我更新,降低其族群數量,以及促使分化。此外,我發現給予大腸癌細胞株 DLD1,常山植物的萃取物處理後,會促進 Egr-1 蛋白質的表現,並且也會降低癌幹細胞的族群數量及特性,代表著常山萃取物可能是透過促進 Egr-1 來達成抑制癌幹細胞的功效。未來可以利用這些藥物,使病患腫瘤組織中,癌幹細胞群減少甚至消失,進而降低癌症的復發以及轉移,增加治療的成功率。 Cancer stem cells (CSCs) are the small population cells in tumor and have the ability of self-renewal to maintain themselves and differentiation into various non-stem cancer cells. CSCs are responsible for tumor progression, drug resistance, metastasis and cancer recurrence. Early growth response-1 (Egr-1), a zinc finger transcription factor, is involved in regulation of cell proliferation, apoptosis and stem cell differentiation. In cancer, Egr-1 has a dual role as both an oncogene and a tumor suppressor. Therefore, Egr-1 may play an important role in CSCs. In this study, I demonstrated that Egr-1 could inhibited self-renewal ability of CSCs to form spheres and colonies. The ratio of side population and colorectal CSCs markers were reduced. In addition, Egr-1 could also suppress drug resistance and migration of CSCs. These data demonstrated that Egr-1 could reduce the number of CSCs in cancer through inhibition of self-renewal and inducing CSCs differentiation. Furthermore, after treatment of Dichroa febrifuga extract, Egr-1 protein expression was upregulated in colorectal cancer cells, and the abilities of CSCs, such as self-renewal and drug resistance, were inhibited. These evidences revealed that Dichroa febrifuga extract had an antitumor effect may associate with the induction of Egr-1. Therefore, Dichroa febrifuga extract might be useful for decreasing or even eliminating CSCs in tumor mass. This method might be a CSCs target therapy to prevent tumor recurrence and metastasis. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79058 |
DOI: | 10.6342/NTU201803179 |
全文授權: | 有償授權 |
電子全文公開日期: | 2023-08-24 |
顯示於系所單位: | 生化科技學系 |
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