Center for Advanced Molecular Imaging and Translation (CAMIT), Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
FASEB J. 2020 Jul;34(7):9678-9693. doi: 10.1096/fj.202000573RR. Epub 2020 May 29.
Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.
多形性胶质母细胞瘤是最常见且侵袭性最强的神经胶质瘤，预后较差。重要的是，胶质母细胞瘤的有效治疗选择尚未满足需求。肥胖和低身体活动与癌症风险增加有关，而运动与癌症发展和进展的延迟有关。流行病学研究表明，运动与胶质母细胞瘤患者的生存率之间存在相关性。然而，运动在胶质母细胞瘤中发挥抗癌作用的机制尚不清楚。在这里，我们发现，运动诱导的肌因子鸢尾素诱导胶质母细胞瘤细胞发生 G1/M 细胞周期阻滞并增加 p21 水平，从而抑制细胞增殖。此外，鸢尾素通过上调 TFPI-2 抑制胶质母细胞瘤细胞侵袭，甚至逆转与癌相关脂肪细胞共培养促进的侵袭性肿瘤表型。此外，鸢尾素延缓了异种移植胶质母细胞瘤肿瘤的生长，放射性标记的鸢尾素在体内表现出特定的肿瘤靶向能力。因此，这项研究确定了运动通过鸢尾素预防癌症进展的一个潜在分子机制。有趣的是，鸢尾素有可能被开发为分子成像和治疗抗癌药物。
