Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy

The pathogenesis of muscle atrophy plays a central role in cancer cachexia, and chemotherapy contributes to this condition. Therefore, the present study aimed to evaluate the effects of endurance exercise on time-dependent muscle atrophy caused by doxorubicin. For this, C57 BL/6 mice were subcutaneo...

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Main Authors: Edson Alves de Lima, Alexandre Abilio de Souza Teixeira, Luana Amorim Biondo, Tiego Aparecido Diniz, Loreana Sanches Silveira, Dario Coletti, Silvia Busquets Rius, José Cesar Rosa Neto
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/11/3466
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author Edson Alves de Lima
Alexandre Abilio de Souza Teixeira
Luana Amorim Biondo
Tiego Aparecido Diniz
Loreana Sanches Silveira
Dario Coletti
Silvia Busquets Rius
José Cesar Rosa Neto
author_facet Edson Alves de Lima
Alexandre Abilio de Souza Teixeira
Luana Amorim Biondo
Tiego Aparecido Diniz
Loreana Sanches Silveira
Dario Coletti
Silvia Busquets Rius
José Cesar Rosa Neto
author_sort Edson Alves de Lima
collection DOAJ
description The pathogenesis of muscle atrophy plays a central role in cancer cachexia, and chemotherapy contributes to this condition. Therefore, the present study aimed to evaluate the effects of endurance exercise on time-dependent muscle atrophy caused by doxorubicin. For this, C57 BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma cells (LLC group). One week after the tumor establishment, a group of these animals initiated the doxorubicin chemotherapy alone (LLC + DOX group) or combined with endurance exercise (LLC + DOX + EXER group). One group of animals was euthanized after the chemotherapy cycle, whereas the remaining animals were euthanized one week after the last administration of doxorubicin. The practice of exercise combined with chemotherapy showed beneficial effects such as a decrease in tumor growth rate after chemotherapy interruption and amelioration of premature death due to doxorubicin toxicity. Moreover, the protein degradation levels in mice undergoing exercise returned to basal levels after chemotherapy; in contrast, the mice treated with doxorubicin alone experienced an increase in the mRNA expression levels of the proteolytic pathways in gastrocnemius muscle (<i>Trim63, Fbxo32, Myostatin, FoxO</i>). Collectively, our results suggest that endurance exercise could be utilized during and after chemotherapy for mitigating muscle atrophy promoted by doxorubicin and avoid the resumption of tumor growth.
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spelling doaj.art-97ed4aec59a34cf2a8b9a167f562e9722023-11-20T21:46:31ZengMDPI AGCancers2072-66942020-11-011211346610.3390/cancers12113466Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following ChemotherapyEdson Alves de Lima0Alexandre Abilio de Souza Teixeira1Luana Amorim Biondo2Tiego Aparecido Diniz3Loreana Sanches Silveira4Dario Coletti5Silvia Busquets Rius6José Cesar Rosa Neto7Immunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, São Paulo 05508-000, BrazilImmunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, São Paulo 05508-000, BrazilImmunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, São Paulo 05508-000, BrazilImmunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, São Paulo 05508-000, BrazilImmunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, São Paulo 05508-000, BrazilBiological Adaptation and Ageing, B2A CNRS UMR 8256, INSERM ERL U1164, Sorbonne Université, 75005 Paris, FranceCancer Research Group, Departament de Bioquímica i Molecular Biomedicine, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, SpainImmunometabolism Research Group, Department of Cell and Developmental Biology, University of São Paulo, São Paulo 05508-000, BrazilThe pathogenesis of muscle atrophy plays a central role in cancer cachexia, and chemotherapy contributes to this condition. Therefore, the present study aimed to evaluate the effects of endurance exercise on time-dependent muscle atrophy caused by doxorubicin. For this, C57 BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma cells (LLC group). One week after the tumor establishment, a group of these animals initiated the doxorubicin chemotherapy alone (LLC + DOX group) or combined with endurance exercise (LLC + DOX + EXER group). One group of animals was euthanized after the chemotherapy cycle, whereas the remaining animals were euthanized one week after the last administration of doxorubicin. The practice of exercise combined with chemotherapy showed beneficial effects such as a decrease in tumor growth rate after chemotherapy interruption and amelioration of premature death due to doxorubicin toxicity. Moreover, the protein degradation levels in mice undergoing exercise returned to basal levels after chemotherapy; in contrast, the mice treated with doxorubicin alone experienced an increase in the mRNA expression levels of the proteolytic pathways in gastrocnemius muscle (<i>Trim63, Fbxo32, Myostatin, FoxO</i>). Collectively, our results suggest that endurance exercise could be utilized during and after chemotherapy for mitigating muscle atrophy promoted by doxorubicin and avoid the resumption of tumor growth.https://www.mdpi.com/2072-6694/12/11/3466doxorubicinchemotherapyendurance exerciseLewis lung carcinomatumorskeletal muscle
spellingShingle Edson Alves de Lima
Alexandre Abilio de Souza Teixeira
Luana Amorim Biondo
Tiego Aparecido Diniz
Loreana Sanches Silveira
Dario Coletti
Silvia Busquets Rius
José Cesar Rosa Neto
Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy
Cancers
doxorubicin
chemotherapy
endurance exercise
Lewis lung carcinoma
tumor
skeletal muscle
title Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy
title_full Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy
title_fullStr Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy
title_full_unstemmed Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy
title_short Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy
title_sort exercise reduces the resumption of tumor growth and proteolytic pathways in the skeletal muscle of mice following chemotherapy
topic doxorubicin
chemotherapy
endurance exercise
Lewis lung carcinoma
tumor
skeletal muscle
url https://www.mdpi.com/2072-6694/12/11/3466
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