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Introduction <p>Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear.</p> Objectives <p>This study investigated ET-induced structural, functional, vascular, oxidative stress, and plausible glucose uptake alterations of the left ventricle (LV) in a murine breast cancer model during DOX treatment.</p> Methods <p>Female FVB/N-mice were divided to tumor-free groups with or without voluntary wheel-running ET and those inoculated subcutaneously with mammary tumor-derived I3TC-cells with or without exercise or DOX treatment (5&#xa0;mg/kg/week). Mice underwent 2-[<sup>18</sup>F]fluoro-2-deoxy-D-glucose positron emission tomography and echocardiography after two and four DOX-doses. The cardiac histology, oxidative stress, maximal metabolic enzyme activities, and mitochondrial respiration were analyzed.</p> Results <p>DOX increased LV glucose uptake (LVGU) and mitochondrial uncoupling and decreased running activity, LV-weight, and ejection fraction (EF). In DOX-treated group ET blunted the increase in LVGU, increased LV-weight and EF, and lowered LV lactate dehydrogenase activity. Exercised mice had lower LVGU compared to unexercised groups and DOX-treated ET-group did not differ from tumor-free ET-group in LV-weight or EF whereas unexercised DOX-treated group did. ET also increased LV citrate synthase activity in tumor-bearing animals. There was an inverse association between LVGU and EF and LV-weight.</p> Conclusion <p>In a murine breast cancer model, voluntary ET moderated DOX-induced cardiotoxicities such as increased LVGU, LV-atrophy and decreased EF. This suggests that ET might benefit patients with cancer undergoing doxorubicin treatment by mitigating cardiotoxicity.</p>

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Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月21日

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  • Tytti-Maria Uurasmaa,
  • Pauline Bourdin,
  • Wail Nammas,
  • Shiva Latifi,
  • Heidi Liljenbäck,
  • Antti Saraste,
  • Olli Eskola,
  • Johan Rajander,
  • Anne Roivainen,
  • Helene Rundqvist,
  • Anu Autio,
  • Ilkka Heinonen,
  • Katja Anttila

摘要

Introduction

Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear.

Objectives

This study investigated ET-induced structural, functional, vascular, oxidative stress, and plausible glucose uptake alterations of the left ventricle (LV) in a murine breast cancer model during DOX treatment.

Methods

Female FVB/N-mice were divided to tumor-free groups with or without voluntary wheel-running ET and those inoculated subcutaneously with mammary tumor-derived I3TC-cells with or without exercise or DOX treatment (5 mg/kg/week). Mice underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography and echocardiography after two and four DOX-doses. The cardiac histology, oxidative stress, maximal metabolic enzyme activities, and mitochondrial respiration were analyzed.

Results

DOX increased LV glucose uptake (LVGU) and mitochondrial uncoupling and decreased running activity, LV-weight, and ejection fraction (EF). In DOX-treated group ET blunted the increase in LVGU, increased LV-weight and EF, and lowered LV lactate dehydrogenase activity. Exercised mice had lower LVGU compared to unexercised groups and DOX-treated ET-group did not differ from tumor-free ET-group in LV-weight or EF whereas unexercised DOX-treated group did. ET also increased LV citrate synthase activity in tumor-bearing animals. There was an inverse association between LVGU and EF and LV-weight.

Conclusion

In a murine breast cancer model, voluntary ET moderated DOX-induced cardiotoxicities such as increased LVGU, LV-atrophy and decreased EF. This suggests that ET might benefit patients with cancer undergoing doxorubicin treatment by mitigating cardiotoxicity.