Endurance training attenuates TNF-α elevation in a murine model of lung adenocarcinoma cachexia: A pilot study
Introduction: Cancer cachexia is a multifactorial syndrome characterized by weight loss, skeletal muscle wasting, and systemic inflammation. Tumor necrosis factor-alpha (TNF-α) plays a central role in cachexia pathophysiology; however, the anti-inflammatory effects of endurance exercise in lung adenocarcinoma–associated cachexia remain insufficiently defined.
Objective: This study aimed to investigate the effects of endurance training on systemic inflammation, as assessed by circulating TNF-α levels, and cachexia-related outcomes in a murine orthotopic model of lung adenocarcinoma.
Methods: Male BALB/cAJcl-nu/nu mice were assigned to four groups: non-exercise control, exercise control, non-exercise lung adenocarcinoma cachexia, and exercise lung adenocarcinoma cachexia (n = 6 per group). An orthotopic lung adenocarcinoma model was established by trans-airway implantation of A549 cells. Endurance training was performed at 20 m/min for 30 min, five days per week for six weeks. Body weight, gastrocnemius wet weight, circulating TNF-α levels, and lung macroscopic and histological findings were evaluated. Data were analyzed using one-way and two-way analyses of variance.
Results: After six weeks, tumor-bearing mice exhibited significant body weight loss and skeletal muscle atrophy compared with controls, confirming successful induction of cachexia. Endurance training partially attenuated body weight loss in tumor-bearing mice. Macroscopic and histological analyses confirmed lung tumor presence in both non-exercise and exercise cachexia groups. Circulating TNF-α levels were significantly elevated in tumor-bearing mice compared with controls; notably, endurance training significantly reduced TNF-α levels in cachexia mice. Two-way analysis revealed significant main effects of tumor burden and exercise on TNF-α levels.
Conclusion: Endurance training attenuates systemic TNF-α elevation in a murine model of lung adenocarcinoma cachexia without suppressing tumor establishment. These findings support endurance exercise as a supportive anti-inflammatory strategy in cancer cachexia.
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