| 研究生: |
呂忠裕 Lee, Chon-Yee |
|---|---|
| 論文名稱: |
介白素二十受器單株抗體於小鼠肝癌模式中抑制介白素二十四功用 Anti-IL-20 Receptor 1 Monoclonal Antibody Inhibits the Function of IL-24 in Mouse Liver 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: | 2013 |
| 畢業學年度: | 101 |
| 語文別: | 中文 |
| 論文頁數: | 71 |
| 中文關鍵詞: | 介白素二十四 、介白素二十 、肝癌 |
| 外文關鍵詞: | IL-24, IL-20, Hepatoma |
| 相關次數: | 點閱:51 下載:0 |
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IL-24隸屬於第二型細胞激素中的IL-10家族的一員。介白素-24的受體是由IL-20R1以及IL-20R2組成的異雙聚體受體 (Heterodimer receptor)。然而,IL-20R1所組成的受體的配位體 (Ligand)除了IL-24外,也包含IL-19以及IL-20。這些配位體都能通過連接IL-20R1受體來達到細胞與細胞間信息的傳遞。
根據實驗室先前的研究,發現IL-19以及IL-20在一些發炎性疾病中扮演重要的角色,如慢性腎臟疾病、類風濕性關節炎以及癌症。根據先前的研究,IL-24生物功能為對廣泛的腫瘤具有抑制其生長及促使腫瘤細胞走向細胞凋亡 (Apoptosis)。而IL-19以及IL-20都有共同的受體為IL-20R1/IL-20R2異雙聚體受體 (Heterodimer receptor)。因此,實驗室建立了IL-20R1受體的單株抗體51D以希望能同時阻斷IL-19以及IL-20的功用而達到治療效果。
我們想要進一步探討利用51D來治療發炎性疾病時,51D會不會同時影響IL-24的抑制癌細胞功能。因此,我們利用小鼠肝癌腫瘤模式,研究51D與IL-24的關係。根據動物實驗結果,IL-24確實能抑制老鼠腫瘤的生長,再給予51D則會影響IL-24的功能而促使腫瘤生長不受到抑制。此外,IL-24也能抑制與發炎反應相關的細胞激素的表現。
除此之外,我們發現IL-20也參與於肝癌的生長與發育過程。當腫瘤細胞給予IL-20單株抗體治療時,也能抑制細胞的生長以及遷徒。在動物實驗結果中,也可以發現IL-20單株抗體能抑制腫瘤的生長。因此,我們證明了IL-24與IL-20同時參與肝癌的生長以及發育。
另外,我們也進行IL-20R1基因剔除老鼠與野生型老鼠的差異分析。根據研究結果發現IL-20R1基因剔除老鼠腹部白色脂肪組織明顯比野生型老鼠來得大且重。因此,我們推測IL-20R1基因剔除老鼠體內的脂肪合成與野生型老鼠可能有所不同。
The receptor of IL-24 is a heterodimer consisting of R1 and R2 subunits. IL-20 R1 can also bind to IL-20, IL19 and IL-24 to activate signal transduction. Our previous studies showed that cytokines binding to IL-20 R1/IL-20 R2 heterodimer are involved in many diseases including chronic kidney disease, rheumatoid arthritis and cancer. IL-24 functions as a tumor suppressor in cancer and is involved in hepatoma and breast cancer. IL-24 can induce apoptosis of cancer cells and inhibit the motility and migration of cancer cells. To develop a potential drug for disease, we have generated the anti-IL-20 R1 monoclonal antibody 51D to block cytokines function. We used mouse liver cancer model to characterize the function of 51D antibody in blocking IL-24 in cancer. From the result of animal study, we found that IL-24 decreased tumor size and tumor weight in mouse hepatoma model. Treatment of 51D antibody inhibits functions of IL-24. Furthermore, expression of pro-inflammatory cytokines also decreased by IL-24.
In addition, we found that IL-20 is also involved in mouse liver cancer. IL-20 antibody inhibited the motility and migration of liver cancer cell. IL-20 antibody decreased tumor size and tumor weight in vivo. We provides evidence that IL-20 and IL-24 shared same receptor subunit in regulating the proliferation and migration of liver cancer.
In addition, we also explored the difference in the phenotype of wild-type and IL-20R1 knock-out mice. The white adipose tissue of IL-20 knockout mice is bigger on the size and heavier on the weight than that of wild-type mice. This result indicates that lipogenesis of IL-20R1 knockout mice maybe different from that of the wild-type mice.
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