Major advances have been made in cancer treatment, but the prognosis for elderly cancer patients with sarcopenia and frailty remains poor. Myokines, which are thought to exert preventive effects against sarcopenia, have been reported to be associated with the prognosis of various cancers, but their effect on head and neck squamous cell carcinoma (HNSCC) is unknown. The aim of this study was to clarify the influence of exercise on the control of HNSCC and to examine the underlying mechanism involved. Mice were injected with HSC-3-M3 cells, a human cell line of highly metastatic and poorly differentiated tongue cancer, at the beginning of the study. Just prior to transplantation, blood was collected from the mice, and the levels of myokines were measured by ELISA. Oncostatin M (OSM), a selected myokine, was added to HSC-3-M3 cells, after which the cell proliferation ability, cell cycle, and protein expression were analyzed in vitro. Tumor cell viability was lower (control: 100%, exercise: 75%), tumors were smaller (control: 26.2 mm3, exercise: 6.4 mm3), and survival was longer in the exercise group than in the control group in vivo. OSM inhibited HSC-3-M3 cell proliferation in a concentration-dependent manner in vitro. The addition of OSM increased the proportion of cells in the G0/G1 phase, decreased the proportion of cells in the G2/M phase, and increased the expression of the CDK inhibitors p21 and p27. These results indicate that exercise may directly inhibit the proliferation of HNSCC cell lines via OSM.
尽管癌症治疗已取得重大进展,但伴有肌肉减少症和衰弱状态的老年癌症患者预后仍然不佳。肌因子被认为对肌肉减少症具有预防作用,已有研究报道其与多种癌症的预后相关,但其对头颈部鳞状细胞癌(HNSCC)的影响尚不明确。本研究旨在阐明运动对HNSCC的调控作用,并探讨其潜在机制。实验开始时向小鼠注射高转移性、低分化的人舌癌细胞系HSC-3-M3。移植前采集小鼠血液,通过酶联免疫吸附法测定肌因子水平。将筛选出的肌因子抑瘤素M(OSM)加入HSC-3-M3细胞后,在体外分析细胞增殖能力、细胞周期及蛋白表达。体内实验显示,运动组较对照组肿瘤细胞活性更低(对照组:100%,运动组:75%)、肿瘤体积更小(对照组:26.2 mm³,运动组:6.4 mm³),且生存期更长。体外实验中,OSM以浓度依赖性方式抑制HSC-3-M3细胞增殖。添加OSM可增加G0/G1期细胞比例,降低G2/M期细胞比例,并上调CDK抑制剂p21和p27的表达。这些结果表明,运动可能通过OSM直接抑制HNSCC细胞系的增殖。
Exercise Suppresses Head and Neck Squamous Cell Carcinoma Growth via Oncostatin M