2-phenylnaphthyridin-4-one 衍生物抑制Interleukin-6誘發人類乳癌上皮細胞轉換為間質細胞之研究

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题名:	2-phenylnaphthyridin-4-one 衍生物抑制Interleukin-6誘發人類乳癌上皮細胞轉換為間質細胞之研究 2-phenylnaphthyridin-4-one derivatives repress Interleukin-6 induces an epithelial–mesenchymal transition phenotype in human breast cancer cells
作者:	徐湘琦
贡献者:	生物科技學系碩士班
关键词:	介白素 EMT;IL-6
日期:	2011-07-26
上传时间:	2011-10-17 16:21:15 (UTC+8)
出版者:	中國醫藥大學
摘要:	乳癌中介白素-6 的含量會隨著腫瘤的增生而提高，而血清中介白素-6 的提升亦和乳癌病患的存活息息相關。上皮細胞和間質細胞轉換的現象包括有E-cadherin 的下降和vimentin 的表現量上升，這些現象會促使癌症轉移並且不利於臨床乳癌。有鑑於此，少數受微環境影響細胞外訊息因子的腫瘤能夠激起上皮細胞和間質細胞轉換已經被印證。在本研究中，我們使用介白素-6 來誘發上皮細胞和間質細胞轉換。因此，我們呈現受到介白素-6 影響的上皮細胞和間質細胞轉換，並提升間質細胞的特徵以及癌症幹細胞的表現。有很多更正面的特徵表現可以歸因於使用2-phenylnaphthyridin-4-one 的衍生物，包括抑制了磷酸化等機制。於此，我們使用了2-phenylnaphthyridin-4-one 的衍生物來抑制受介白素-6 誘發的上皮細胞和間質細胞轉換的現象，以及藉由抑制Jak2/STAT3 訊息途徑的癌症幹細胞的特徵。LYF-11 能夠有效抑制受到介白素-6 誘發E-cadherin 的下降還有vimnentin 的上升，其中是藉由調Jak2/STAT3 磷酸化訊息途徑。簡言之，我們的實驗結果呈現了介白素-6 接受器活性和磷酸化STAT3 表現之間的關聯，且指出LYF-11 對於治療乳癌主要是藉由標定Jak2/STAT3 訊息途徑中是具有潛力的化合物。 Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated serum IL-6 correlates with poor breast cancer patient survival. Epithelial–mesenchymal transition (EMT) phenotypes such as impaired E-cadherin expression or aberrant vimentin induction are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, few tumor microenvironment-derived extracellular signaling factors capable of provoking such a phenotypic transition have been identified. In this study, we showed that IL-6 exhibited an EMT phenotype characterized. Moreover, we report that the induction of an EMT by IL-6 results in the acquisition of mesenchymal traits and in the expression of cancer stem cells (CSCs) markers. Many beneficial properties have been attributed to 2-phenylnaphthyridin-4-one derivatives, including inhibition of tubulin polymerization etc. Here, we found that 2-phenylnaphthyridin-4-one derivatives could repress IL-6 induced EMT phenotype and cancer stem cell markers through repressing Jak2/STAT3 signaling pathway. LYF-11 also effectively inhibited IL6-induced decrease of E-cadherin and increase of vimentin via down-regulation of phosphorylated Jak2 and STAT3. Briefly, our results suggest that a connection between IL-6 receptor activity and phospho-STAT3 protein expression, and suggest that LYF-11 is a potential compound for breast cancer therapy by targeting major components of Jak2/STAT3 signaling pathway.
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