Characterization of a composite fatigue-like phenotype after Lewis lung carcinoma resection followed by low-dose cisplatin in mice.

Fatigue-like impairment after cancer surgery occurs within a complex treatment context, yet experimental preparations that incorporate tumor history, resection, and postoperative treatment remain limited. This study characterized a composite fatigue-like phenotype after subcutaneous Lewis lung carcinoma (LLC) resection followed by low-dose cisplatin. Male C57BL/6J mice were assigned to Blank, Sham, Surgery, and Model groups (n=10/group). The Surgery group underwent LLC inoculation, complete tumor resection, and postoperative saline, whereas the Model group underwent the same procedures followed by cisplatin (2 mg/kg on postoperative days 1 and 4). Body weight, grip strength, treadmill performance, open-field activity, and hepatic and skeletal muscle glycogen were assessed. Serum IL-5, IL-6, IL-10, and TNF-α were explored in three randomly selected mice per group and in an exploratory clinical cohort comprising 5 postoperative patients with lung cancer and 5 control participants. The Model group exhibited a broader multidomain impairment than the Surgery group, characterized by greater postoperative body-weight loss, reduced motor performance and exercise endurance, altered spontaneous locomotor behavior, and reduced peripheral glycogen stores. In the three mice sampled per group, Model mice also showed higher IL-5 and IL-6 concentrations, lower TNF-α concentrations, and similar IL-10 concentrations. In the human cohort, IL-6 showed higher concentrations in postoperative patients than in controls, directionally consistent with the mouse findings, whereas IL-5 and IL-10 did not show a consistent cross-species pattern. Thus, LLC resection followed by low-dose cisplatin was associated with a multidomain fatigue-like functional phenotype.