Physical Exercise Enhances Doxorubicin Response and Attenuates Hepatic Toxicity in a Murine Model of Sarcoma

All articles of this category (opens in new window) Address for correspondence Laura Martins Soares Cortez (lauramsc3@gmail.com) Introduction: Cancer remains one of the leading public health challenges worldwide. Although chemotherapy is widely used in oncological treatment, tumor resistance continues to pose a major obstacle to its effectiveness. In this context, physical exercise has emerged as a promising neoadjuvant strategy, with the potential to enhance tumor sensitivity and optimize the therapeutic outcomes of chemotherapy . Objective: This study investigated the effects of aerobic exercise, alone or in combination with doxorubicin, on tumor and liver parameters in an experimental model of sarcoma . Methods: Swiss mice were divided into four experimental groups: negative control (NC), chemotherapy with doxorubicin (DOX), aerobic exercise only (EX), and a combination of exercise with doxorubicin (EXDOX). Animals in the EX and EXDOX groups underwent an aerobic exercise protocol (60–80% of Vmax, 30 minutes per day for 10 days). Chemotherapy consisted of three administrations of doxorubicin at a dose of 2 mg/kg of body weight per cycle. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test (p<0.05) . Results: There were no significant differences in body weight variation among the groups (p>0.05). Tumor mass was significantly lower in the DOX (1.101±0.196 g), EX (0.674±0.1401 g), and EXDOX (0.847±0.125 g) groups compared to the NC group (2.23±0.135 g) (NC vs. DOX, NC vs. EX, and NC vs. EXDOX: p<0.0001). No significant differences were observed among DOX, EX, and EXDOX (p>0.05). Tumor density was also significantly reduced in the EX (0.410±0.114) and EXDOX (0.349±0.058) groups compared to NC (1.275±0.125) and DOX (1.074±0.102) (NC vs. EX: p<0.0001; NC vs. EXDOX: p<0.0001; DOX vs. EX: p=0.0012; DOX vs. EXDOX: p=0.0007). No difference was found between EX and EXDOX (p=0.977). The hepatosomatic index was higher in the DOX group (0.052±0.001) compared to the EX (0.040±0.001; p=0.005) and EXDOX (0.040±0.002; p=0.009) groups . Conclusion: Aerobic exercise reduced both tumor mass and density in a murine sarcoma model. When combined with doxorubicin, exercise not only enhanced the antitumor effects but also mitigated liver-related side effects, as indicated by the lower hepatosomatic index. These findings highlight the potential of physical exercise as a therapeutic option in oncology, supporting both the efficacy and safety of chemotherapy treatment. Publication History Article published online: 26 June 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/) Thieme Revinter Publicações Ltda. Rua Rego Freitas, 175, loja 1, República, São Paulo, SP, CEP 01220-010, Brazil Bibliographical Record Laura Martins Soares Cortez, Jorddam Almondes Martins, Thiago Sousa Reinaldo, Aureliano Machado de Oliveira, Laissa Lindes Sousa Feitoza, Silvia Letícia Maciel Barbosa, Juliana Soares Severo, Paulo Michel Pinheiro Ferreira, Francisco Leonardo Torres-Leal. Physical Exercise Enhances Doxorubicin Response and Attenuates Hepatic Toxicity in a Murine Model of Sarcoma. Brazilian Journal of Oncology 2026; 22. DOI: 10.1055/s-0046-1825446