2019-01-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/697411摘要：運動已知有益健康外，也會防止癌症、代謝疾病及心血管疾病的發生。運動不只可防止癌症發生，也會延遲癌症的進程及促進治療效果。然而，目前對於運動是如何達到此一作用，仍不甚清楚。許多因運動而分泌的胜&#32957;或運動細胞激素，都曾被提出可能是運動延緩癌症進程的關鍵，但目前尚無確實的實驗結果支持此一論點。我們於此計畫中，提出irisin會預防癌症的發生且irisin極為可能為運動影響癌症發生的重要因素之一。我們發現在多型性神經膠母細胞瘤病人中，FNDC5 (irisin的前驅物) 表現量低於正常腦組織，所以在此計畫中要研究irisin對於多型性神經膠母細胞瘤細胞株的影響，多型性神經膠母細胞瘤是屬於極為惡性且普遍的腦瘤，其病人生存率通常不到1年。因此，開發新的治癌方法極為重要。首先，我們發現純化的irisin會引發多型性神經膠母細胞瘤細胞週期停滯進而抑制細胞生長。此外，irisin也會抑制癌細胞移動及侵襲能力。在此計畫，更將進一步以全轉錄體分析篩選出多個基因，並深入分析這些基因是否參與於irisin抑制癌細胞生長及侵襲的路徑中。最重要的是，在此計劃中，初步測試顯示irisin抑制小鼠腫瘤的生長，未來要繼續完整的研究，以評估irisin作為治癌藥物的可能性，進而以研發出對多型性神經膠母細胞瘤的新治療方式，且由本計畫的結果提出運動為何能預防癌症發生的可能機制。<br> Abstract: Exercise is beneficial for human health and also prevents development of cancer, metabolic diseases and cardiovascular diseases. Exercise not only prevents cancer initiation, but also delays cancer progression and improves cancer therapeutic effects. However, the molecular mechanism of how exercise delays cancer progression is still not clear. Many exercise-induced factors, including cytokines, peptides, and hormones, have been proposed as the key for delaying cancer progression. None of them had the concrete results yet. Here, we propose that irisin, the exercise-induced myokine, plays a key role in cancer prevention and is one of reasons why exercise delays cancer development. Moreover, because lower gene expression of FNDC5, the precursor of irisin, in glioblastoma patients, in this study, the irisin effects on glioblastoma are investigated. Glioblastoma is the most common and aggressive brain tumor type, and the survival rate of glioblastoma is less than one year. Hence, the new therapeutic approach is in urgent need. First, we observe that the purified recombinant human irisin reduced glioblastoma cell growth due to cell cycle arrest. Next, irisin also inhibits glioblastoma cell invasion. Moreover, to decipher the detailed molecular mechanism of irisin effects on glioblastoma cell proliferation and cell invasion, several genes selected from transcriptome analysis will be further investigated. Last but not the least, the above results will be further verified in in vivo tumor models. The results of the project help us to develop the new strategy for cancer therapy and decipher the molecular mechanism of how exercise prevents cancer development.運動肌肉激素irisin多型性神經膠母細胞瘤細胞侵襲Exercisemyokineirisinglioblastomacell invasion