運動預防癌症的效益：可誘導腫瘤細胞凋亡之肌肉激素

Effects of Exercise on Cancer Prevention: Apoptosis of Tumor Cells Induced by Myokines

10.6162/SRR.2017.141.07

黃森芳(Sen-Fang Huang)；陳聰毅(Tsung-I Chen)；黃國欽(Kuo-Chin Huang)

規律運動 ； 肌肉收縮 ； 動機 ； regular exercise ； muscle contraction ； motivation

大專體育

141期（2017 / 06 / 30）

52 - 59

繁體中文

流行病學研究證實，規律運動可以降低某些癌症的罹患風險，但其可能的作用機轉目前尚未清楚。本文旨在探討經身體活動或運動時肌肉收縮所分泌的肌肉肌素，可能會誘導腫瘤細胞產生自發性凋亡作用。研究方法是從PubMed 蒐尋相關文獻，以輸入關鍵詞：exercise、myokines、cancer、apoptosis 等，歸納整理後發現，目前主要有四種肌肉激素：黏骨素、抑瘤素M、鳶尾素與鈣衛蛋白皆會誘發腫瘤細胞凋亡的作用，這現象可能是運動可預防癌症的重要因素之一。綜合評析後所得結語如下：肌肉激素可能藉由誘導腫瘤細胞凋亡，以抑制癌組織之發展。這些肌肉激素，大都須藉由運動中肌肉的收縮，才會增加分泌並釋放進入血液循環中，對癌症預防才具有關鍵之功效。透過本文論述，藉此提供大眾對於預防癌症策略有更多選擇性，並提高運動之動機。

Epidemiological studies suggested that regular exercise may reduce the morbidity risks of some cancers. However, the mechanism by which exercise may prevent cancers is still unclear. The purpose of this article is to explore possible mechanisms by which exercise brings myokines to induce the apoptosis of tumor cells with the potential effect of cancer prevention. After searching PubMed for related key words, including exercise, myokines, cancer and apoptosis, we found that recent studies demonstrated that some cytokines secreted by muscle are so-called myokines. Four basic kinds of myokines, including osteonectin, oncostatin M (OSM), irisin, and calprotectin, are capable of inducing the apoptosis of cancer cells. Skeletal muscle contraction during exercise stimulates the elevated secretion of myokines into the blood circulation, restraining the development of cancer cells. This phenomenon may be the key underlying mechanism by which exercise may prevent or inhibit cancer. This review article may provide more choices and strategies for preventing some forms of cancer and generating motivation for exercise.

1. 衛生福利部（2014）。102 年死因統計結果分析。資料引自http://www.mohw.gov.tw/dl-4913-447a09db-0d99-4a44-8c1b-ca156ee12ec8.html[Ministry of Health and Welfare. (2014). Statistics of causes of death 2013. Retrieved from http://www.mohw.gov.tw/dl-4913-447a09db-0d99-4a44-8c1bca156ee12ec8.html]
2. Aoi, W.,Naito, Y.,Takagi, T.,Tanimura, Y.,Takanami, Y.,Kawai, Y.,Yoshikawa, T.(2013).A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise.Gut,62(6),882-889.
3. Argilés, J. M.,López-Soriano, F. J.,Busquets, S.(2009).Therapeutic potential of interleukin-15: A myokine involved in muscle wasting and adiposity.Drug Discovery Today,14(3-4),208-213.
4. Berntzen, H. B.,Fagerhol, M. K.(1990).L1, a major granulocyte protein; isolation of high quantities of its subunits.Scandinavian Journal of Clinical and Laboratory Investigation,50(7),769-774.
5. Bortoluzzi, S.,Scannapieco, P.,Cestaro, A.,Danieli, G. A.,Schiaffino, S.(2006).Computational reconstruction of the human skeletal muscle secretome.Proteins,62(3),776-792.
6. Boström, P.,Wu, J.,Jedrychowski, M. P.,Korde, A.,Ye, L.,Lo, J. C.,Spiegelman, B. M.(2012).A PGC1- alpha-dependent myokine that drives brown-fatlike development of white fat and thermogenesis.Nature,481(7382),463-468.
7. Ehrchen, J. M.,Sunderkötter, C.,Foell, D.,Vogl, T.,Roth, J.(2009).The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity and cancer.Journal of Leukocyte Biology,86(3),557-566.
8. Fagerhol, M. K.,Nielsen, H. G.,Vetlesen, A.,Sandvik, K.,Lyberg, T.(2005).Increase in plasma calprotectin during long-distance running.Scandinavian Journal of Clinical and Laboratory Investigation,65(3),211-220.
9. Gannon, N. P.,Vaughan, R. A.,Garcia-Smith, R.,Bisoffi, M.,Trujillo, K. A.(2015).Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro.International Journal of Cancer,136(4),E197-E202.
10. Garber, K.(2012).Explaining exercise: Cellular "selfeating" may account for some benefits of exercise.Science,335(6066),281.
11. Ghavami, S.,Kerkhoff, C.,Los, M.,Hashemi, M.,Sorg, C.,Karami-Tehrani, F.(2004).Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: The role of ROS and the effect of metal ions.Journal of Leukocyte Biology,76(1),169-175.
12. Goh, J.,Niksirat, N.,Campbell, K. L.(2014).Exercise training and immune crosstalk in breast cancer microenvironment: Exploring the paradigms of exercise-induced immune modulation and exercise-induced myokines.American Journal of Translational Research,6(5),422-438.
13. Hojman, P.,Dethlefsen, C.,Brandt, C.,Hansen, J.,Pedersen, L.,Pedersen, B. K.(2011).Exerciseinduced muscle-derived cytokines inhibit mammary cancer cell growth.American Journal of Physiolology. Endocrinology and Metabolism,301(3),E504-E510.
14. Kerr, J. F.,Wyllie, A. H.,Currie, A. R.(1972).Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics.British Journal of Cancer,26(4),239-257.
15. Lee, P.,Linderman, J. D.,Smith, S.,Brychta, R. J.,Wang, J.,Idelson, C.,Celi, F. S.(2014).Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans.Cell Metabolism,19(2),302-309.
16. Liu, Y. P.,Hsiao, M.(2013).Exercise-induced SPARC prevents tumorigenesis of colon cancer.Gut,62(6),810-811.
17. Lu, Y.,Li, H.,Shen, S.-W.,Shen, Z.-H.,Xu, M.,Yang, C.-J.,Qi, H.-J.(2016).Swimming exercise increases serum irisin level and reduces body fat mass in high-fat-diet fed Wistar rats.Lipids in Health and Disease,15,93.
18. Ludlow, A. T.,Ludlow, L. W.,Roth, S. M.(2013).Do telomeres adapt to physiological stress? Exploring the effect of exercise on telomere length and telomere-related proteins.BioMed Research International,2013
19. McTiernan, A.(2008).Mechanisms linking physical activity with cancer.Nature Reveiws. Cancer,8(3),205-211.
20. Mortensen, O. H.,Andersen, K.,Fischer, C.,Nielsen, A. R.,Nielsen, S.,Akerström, T.,Pedersen, B. K.(2008).Calprotectin is released from human skeletal muscle tissue during exercise.The Journal of Physiology,586(14),3551-3562.
21. Pedersen, B. K.,Akerström, T. C.,Nielsen, A. R.,Fischer, C. P.(2007).Role of myokines in exercise and metabolism.Journal of Applied Physiology,103(3),1093-1098.
22. Pedersen, B. K.,Febbraio, M. A.(2012).Muscles, exercise and obesity: Skeletal muscle as a secretory organ.Nature Reviews. Endocrinology,8(8),457-465.
23. Reisi, J.,Ghaedi, K.,Rajabi, H.,Marandi, S. M.(2016).Can resistance exercise alter irisin levels and expression profiles of FNDC5 and UCP1 in rats?.Asian Journal of Sports Medicine,7(4),e35205.
24. Shao, L.,Li, H.,Chen, J.,Song, H.,Zhang, Y.,Wu, F.,Tang, D.(2017).Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition.Biochemical and Biophysical Research Communications,485(3),598-605.
25. So, B.,Kim, H.-J.,Kim, J.,Song, W.(2014).Exerciseinduced myokines in health and metabolic diseases.Integrative Medicine Research,3(4),172-179.
26. Striz, I.,Trebichavský, I.(2004).Calprotectin -A pleiotropic molecule in acute and chronic inflammation.Physiological Research,53(3),245-253.
27. Tanaka, M.,Miyahima, A.(2003).Onconstatin M, a multifunctional cytokine.Reviews of Physiology, Biochemistry and Pharmacology,149,39-52.
28. Winn, N. C.,Grunewald, Z. I.,Liu, Y.,Heden, T. D.,Nyhoff, L. M.,Kanaley, J. A.(2017).Plasma irisin modestly increases during moderate and highintensity afternoon exercise in obese females.PLoS One,12(1),e0170690.
29. World Cancer Research Fund,American Institute for Cancer Research(2007).Food, Nutrition, Physical Activity, and the Prevention of Cancer: A global perspective.Washington, DC:Author.
30. Yan, Q.,Sage, E. H.(1999).SPARC, a matricellular glycoprotein with important biological functions.The Journal of Histochemistry & Cytochemistry: Official journal of the Histochemistry Society,47(12),1495-1505.
31. Yui, S.,Mikami, M.,Yamazaki, M.(1995).Induction of apoptotic cell death in mouse lymphoma and human leukemia cell lines by a calcium-binding protein complex, calprotectin, derived from inflammatory peritoneal exudate cells.Journal of Leukocyte Biology,58(6),650-658.
32. Zhao, J.,Su, Z.,Qu, C.,Dong, Y.(2017).Effects of 12 weeks resistance training on serum irisin in older male adults.Frontiers in Physiology,8,171.
33. 譚健民(2009)。粒線體與細胞凋亡。生物醫學，2(3)，250-272。

1. 盧寶芬,劉昆祐,馬上鈞(2022)。大專時期參與運動團隊與畢業後規律運動的關係。大專體育，163，11-29。