請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53727
標題: | 探討Protocadherin 10對大腸直腸癌細胞之細胞凋亡和幹細胞特性之影響 The effects of Protocadherin 10 on apoptosis and stemness in colorectal cancer |
作者: | Yu-Lin Hung 洪佑霖 |
指導教授: | 楊雅倩(Ya-Chien Yang) |
關鍵字: | 大腸直腸癌,PCDH10,細胞凋亡,癌幹化能力, Colorectal cancer,PCDH10,Apoptosis,Cancer stemness, |
出版年 : | 2015 |
學位: | 碩士 |
摘要: | 大腸直腸癌於美國及台灣之癌症致死原因皆排名第三名,其致死原因主要是由於遠端器官轉移,其容易轉移之器官包括肝臟及肺臟。雖然至今陸續發展多種抗癌療法或改進之合併性治療,但預後差之事實依然存在,故鑑定出此癌症之分子機轉仍有助於其診斷與治療。實驗室近幾年之研究透過細胞增生、非貼附性生長、遷移、侵襲等體外試驗,以及動物試驗利用異種移植模型進行腫瘤生成及肝臟轉移分析,其結果皆顯示PCDH10於大腸直腸癌扮演抑癌基因之角色。本論文主要分為三部分探討,首先證實PCDH10能增加大腸癌細胞自發性細胞凋亡外,於高氧化壓力環境下亦可明顯促進細胞凋亡;第二部分則以癌幹細胞特性為主題,結果發現PCDH10可減少癌細胞球狀體形成之比例,且能抑制其癌幹細胞標記CD133、Bmi-1、Nanog及Sox2之表現;第三部份則進一步探討PCDH10傳遞路徑調控細胞凋亡及癌細胞幹化能力之分子機轉,結果顯示:PCDH10透過抑制PI3K/AKT及Sonic Hedgehog訊息傳遞路徑之活化達到促進細胞凋亡及抑制癌幹細胞之潛能。綜合以上結果,我們更加確認PCDH10於大腸直腸癌扮演重要的抑癌角色並揭露其調控機制。 Colorectal cancer (CRC) is the third leading cause of cancer death in the United states and Taiwan. Most deaths of CRC are associated with distant metastasis, including liver and lung. Although recent researches have acclaimed that many alternative treatments to attenuate tumor progression, but not always get good prognosis. Therefore, an improved understanding of the molecular mechanism involved in CRC may provide new insights into CRC diagnosis and treatment. In previous studies , we demonstrated that PCDH10 is a crucial tumor suppressor gene in CRC by cell proliferation, anchorage-independent growth, migration and invasion assay in vitro. Moreover, we also performed tumorigenesis and liver metastasis experiments with in vivo xenograft tumor models. The results confirmed that PCDH10 is a CRC-associated tumor suppressor gene. In the study, there are three specific aims. The first was focused on the role of PCDH10 in regulation of apoptosis. The results indicated that PCDH10 increased not only spontaneous apoptosis, but also oxidative stress-induced apoptosis. The second part was focused on the effect of PCDH10 on cancer stemness. The results showed that re-expression of PCDH10 decreased spheroid formation and down-regulated cancer stem cell markers, including CD133, Bmi-1, Nanog and Sox2 in CRC cells. In the third part, we investigated the pathways involved in PCDH10-modulated apoptosis and stemness potential. The results revealed that PCDH10 might down-regulate PI3K/AKT and Sonic Hedgehog signaling pathways to induce apoptosis and inhibit stemness potential. Taken together, we further confirm that PCDH10 plays a crucial role in tumor suppression and disclose the molecular mechanisms regulated by PCDH10. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53727 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學檢驗暨生物技術學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-104-1.pdf 目前未授權公開取用 | 5.8 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。