| 研究生: |
郭鵬輝 Kwok, Franky Antonius |
|---|---|
| 論文名稱: |
介白素十九與食道癌的研究 Study of IL-19 and Esophageal Cancer |
| 指導教授: |
張明熙
Chang, Ming-Shi |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 生物化學暨分子生物學研究所 Department of Biochemistry and Molecular Biology |
| 論文出版年: | 2011 |
| 畢業學年度: | 99 |
| 語文別: | 英文 |
| 論文頁數: | 67 |
| 中文關鍵詞: | 細胞激素 、介白素-19 、食道癌 、CE81T |
| 外文關鍵詞: | cytokines, interleukin-19, esophageal cancer, CE81T |
| 相關次數: | 點閱:72 下載:0 |
| 分享至: |
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食道癌是全球排名第六的致命癌症,全球大約有386,000人因為食道癌而死亡。在2008年,食道鱗狀細胞癌在台灣男性癌症死亡率排名第六。介白素-19是介白素-10家族中的一員,主要是由單核球所分泌。目前已知介白素-19參與許多發炎反應疾病的病程,像是牛皮癬、氣喘以及類風濕性關節炎等。近幾年,有越來越多的研究指出癌細胞本身分泌的細胞激素可以影響腫瘤的生長。在實驗室先前的研究也發現,在食道癌病人的組織切片上可偵測到介白素-19的存在。然而IL-19在食道癌中扮演的角色目前仍尚未清楚,因此,我們想要去探討介白素-19與食道癌之間的關聯性為何。在實驗上,首先,我們利用免疫組織染色法分別在CE81T這株人類的食道癌細胞上偵測到介白素-19以及其兩個受體的蛋白質表現。在細胞增生能力分析結果發現介白素-19可以促進CE81T細胞的生長而介白素-19的單株抗體和介白素-19的受體IL-20R1的單株抗體 (7GW & 51D)則可以抑制CE81T細胞的生長。介白素-19也會誘導CE81T細胞內P-38,JNK,ERK1/2,Akt以及NF-B等訊息傳遞分子的磷酸化。而在形成軟瓊脂集落 (Soft agar colony formation) 實驗中,我們觀察到介白素-19會促進CE81T細胞的集落形成而介白素-19的單株抗體和介白素-19的受體IL-20R1的單株抗體 (7GW & 51D)則可以抑制CE81T細胞的集落形成。另外,介白素-19也會促進CE81T細胞內的TGF-β,Cyclin B1,CXCR4以及MMP-1基因的表現量上升。介白素-19也會促進CE81T細胞的遷移能力而介白素-19的單株抗體和介白素-19的受體IL-20R1的單株抗體 (7GW & 51D)則可以抑制CE81T細胞的遷移能力。而在動物實驗中也可以觀察到,介白素-19的抗體,1BB1,可以藉由降低介白素-19的表現進而抑制腫瘤細胞的生長並且降底TGF-β,CXCR4,CXCL12以及MMP1基因的表現量。總結,我們的實驗證明介白素-19在食道癌的致病過程中扮演重要的角色。
Esophageal cancer is ranked as the sixth most deadly cancer, with 386,000 deaths per year worldwide. In Taiwan, esophageal squamous cell carcinoma (ESCC) was the sixth most common cause of cancer deaths in males in 2008. IL-19 is a member of IL-10 family that is mainly produced by monocytes. IL-19 is involved in the pathogenesis of various inflammatory diseases such as psoriasis, asthma and rheumatoid arthritis. However, the biological functions of IL-19 in esophageal cancer are not well understood. In this study, we aimed to investigate the association of IL-19 with esophageal cancer. Our study showed that IL-19 and its receptors were expressed in the human esophageal cancer cell line CE81T and tissue micro-array using immunohistochemistry (IHC) staining. MTT assays showed that IL-19 promoted the proliferation of CE81T cell which was neutralized by IL-19 monoclonal antibody (1BB1) and IL-20R1 monoclonal antibody (7GW & 51D). IL-19 also induced phosphorylation of P-38, JNK, ERK1/2, Akt and NF-B in CE81T cells. Soft agar colony formation assay showed IL-19 enhanced colony formation of CE81T cells which was neutralized by IL-19 antibody (1BB1) and its receptor IL-20R1 antibody (51D and 7GW). Real time PCR analysis showed that IL-19 induced TGF-β, Cyclin B1, CXCR4 and MMP-1 in CE81T cells. In addition, IL-19 promoted migration in CE81T cell and was neutralized by IL-19 monoclonal antibody (1BB1) and IL-20R1 monoclonal antibody (7GW & 51D). In vivo, 1BB1 reduced tumor growth and down-regulated TGF-β, CXCR4, CXCL12 and MMP1 expression in CE81T tumor bearing mice. In conclusion, this study provides evidence that IL-19 is involved in the pathogenesis of esophageal cancer.
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校內:2021-12-31公開