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

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

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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. DOX-treated exercised mice did not differ from tumor-bearing group without DOX in LVGU or from the 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.

Original languageEnglish
Pages (from-to)89
JournalJournal of Translational Medicine
Volume23
Issue number1
DOIs
Publication statusPublished - 21 Jan 2025
MoE publication typeA1 Journal article-refereed

Keywords

  • Animals
  • Doxorubicin/adverse effects
  • Female
  • Physical Conditioning, Animal
  • Breast Neoplasms/pathology
  • Oxidative Stress/drug effects
  • Mice
  • Glucose/metabolism
  • Cell Line, Tumor
  • Heart Ventricles/drug effects
  • Positron-Emission Tomography

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