請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78099
標題: | 設計並探討具高度安全性及標靶功能的奈米藥物於治療乳癌的成效 A Safety Enhanced, Integrin αvβ3 Targeting Nanodrug for MCF-7 Human Breast Cancer Cells |
作者: | Yin Lun Lau 劉彥麟 |
指導教授: | 何佳安 |
關鍵字: | 修飾白藜蘆醇的硬脂酸,微脂體,組合蛋白αvβ3,阿黴素,熱休克蛋白27, Resveratrol-modified stearate,Liposome,Integrin αvβ3,Doxorubicin,Heat shock protein 27, |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | 白藜蘆醇(Resveratrol)是一個擁有抗癌效果的天然物質,可以從多種植物取得。在過去研究中,將白藜蘆醇修飾在硬脂酸上可以與其他磷脂一起形成微脂體。因為白藜蘆醇能夠與腫瘤相關的組合蛋白αvβ3進行結合,因此我們預計白藜蘆醇修飾在硬脂酸上可以增加微脂體到達腫瘤區域的能力。在本研究中我們著重於開發出一個有優良抗癌功能的奈米藥物去抑制人類乳癌細胞株MCF-7的生長。我們嘗試利用修飾上白藜蘆醇的硬脂酸(Resveratrol-modified stearate,RMS)去合成微脂體(RMS-Lipo),並在微脂體內包覆阿黴素(Doxorubicin),製備出RMS-Lipo-Dox,藉此標靶含有組合蛋白αvβ3活化態的MCF-7細胞。於細胞毒殺實驗結果中顯示,當MCF-7細胞受到RMS比例越高的RMS-Lipo-Dox處理後,MCF-7細胞的存活率就越低;在組合蛋白αvβ3表現量低的乳癌細胞株MDA-MB-231,則沒有明顯的RMS效應。過去文獻發現,白藜蘆醇可以經由減少熱休克蛋白27(hsp27)的表現,並誘導ERK1/2和p53磷酸化去抑制癌細胞生長。所以,我們預測當RMS接上組合蛋白αvβ3,可以誘導下游路徑的產生,促進MCF-7細胞凋亡。在目前西方墨點法的結果中可以得知,修飾在硬脂酸上的白藜蘆醇可以誘導hsp27的表現量明顯下降,表示細胞失去它的保護作用,會更容易被阿黴素所毒殺。歸納以上的實驗結果,我們發現利用修飾白藜蘆醇的硬脂酸可以誘導其下游的訊息傳遞,有效地提高包覆阿徽素的微脂體的治療效果。由此我們認為RMS-Lipo-Dox有潛力被使用在各種大量表現組合蛋白αvβ3的癌症治療上。 Resveratrol, a natural polyphenol compound, is extracted from various plants. It has been investigated long on its chemopreventive activity against human cancer. In the past, research found that resveratrol was able to modify on stearic acid to expand the usage of resveratrol, which can form liposome with other phospholipids. While resveratrol can bind to integrin αvβ3, which was tumor-associated, we hypothesized resveratrol on the surface can render liposome a targeting ability to tumor environment. In this study, we tried to develop a nanodrug with remarkable antiproliferative activity on MCF-7, human breast cancer cell line. Herein, we used resveratrol modified stearate (RMS) as one of the constituents to prepare doxorubicin-encapsulating liposomes (RMS-Lipo-Dox). This nanoformulation would specifically bind to activated integrin αvβ3, resulted in the enhanced cytotoxicity of Dox on MCF-7 through signaling pathways triggered by RMS. From cytotoxicity assays, MCF-7 treated with increasing percentage of RMS-Lipo-Dox exhibited decreasing cell viability, but not another breast cancer cell line, MDA-MB-231, expressing low level of integrin αvβ3. Furthermore, it was reported that resveratrol can reduce expression of Hsp27 in MCF-7 cells. Our immunoblotting results showed the expression of heat shock protein 27 (hsp27) decreased after treated with 7.5% RMS-Lipo. This implied that MCF-7 cells lost protection to environmental stress and became more vulnerable to Dox. Summarizing these results above, we demonstrated that RMS-Lipo-Dox can induce MCF-7 cells apoptosis through downregulation of hsp27, which enhanced cytotoxicity of liposomal Dox. We proposed that RMS-Lipo-Dox is a potential therapeutic agent on integrin αvβ3-overexpressed cancers. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78099 |
DOI: | 10.6342/NTU201602759 |
全文授權: | 有償授權 |
顯示於系所單位: | 生化科技學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-105-R03b22029-1.pdf 目前未授權公開取用 | 2.7 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。