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Clinical and Experimental Medicine

, Volume 17, Issue 2, pp 151–160 | Cite as

Effects of lifelong exercise training on mammary tumorigenesis induced by MNU in female Sprague–Dawley rats

  • Ana I. Faustino-RochaEmail author
  • Adelina Gama
  • Paula A. Oliveira
  • Antonieta Alvarado
  • Maria J. Neuparth
  • Rita Ferreira
  • Mário Ginja
Original Article

Abstract

Breast cancer is the most common malignancy in women worldwide. Several studies have suggested that exercise training may decrease the risk of breast cancer development. This study aimed to evaluate the effects of long-term exercise training on mammary tumorigenesis in an animal model of mammary cancer. Fifty female Sprague–Dawley rats were randomly divided into four groups: MNU sedentary, MNU exercised, control sedentary and control exercised. Animals from MNU groups received an intraperitoneal administration of N-methyl-N-nitrosourea (MNU). Animals were exercised on a treadmill during 35 weeks. When animals were killed, blood samples were collected to determine the hematocrit and to perform the biochemical analysis. Mammary tumors were collected and histologically evaluated; the expression of ERs α and β was evaluated in tumor sections by immunohistochemistry. All survived animals from both MNU groups developed mammary tumors. The number of mammary tumors (p > 0.05) and lesions (p = 0.056) was lower in MNU exercised than in MNU sedentary animals. MNU exercised animals showed lower number of malignant lesions than MNU sedentary animals (p = 0.020). C-reactive protein serum concentration was lower in exercised animals; however, the levels of 17-β estradiol were higher in exercised animals. Tumors from exercised animals exhibited higher expression of ER α than tumors from sedentary animals (p < 0.05). This study analyzes the impact of the longest exercise training protocol on mammary tumorigenesis ever performed. We concluded that the lifelong endurance training has beneficial effects on mammary tumorigenesis in female rats (reduced the inflammation, the number of mammary tumors and lesions, and histological grade of malignancy). Additionally, the mammary tumors from MNU exercised group exhibited higher immunoexpression of ER α that is an indicator of well-differentiated tumors and better response to hormone therapy.

Keywords

Estradiol Estrogen receptors Exercise Mammary tumors MNU 

Abbreviations

MNU

N-methyl-N-nitrosourea

ER

Estrogen receptor

MI

Mortality index

V

Tumors’ volume

IL

Interleukin

CRP

C-reactive protein

H&E

Hematoxylin and eosin

SD

Standard deviation

HDL

High-density lipoprotein

LDL

Low-density lipoprotein

ALT

Alanine aminotransferase

CK

Creatine kinase

Notes

Acknowledgments

This work was supported by European Investment Funds by FEDER/COMPETE/POCI—Operational Competitiveness and Internationalization Program, under project POCI-01-0145-FEDER-006958, and Portuguese Foundation for Science and Technology (FCT), under the project UID/AGR/04033/2013, the project PTDC/DES/114122/2009 and post-graduation grant SFRH/BD/102099/2014.

Authors’ contributions

All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Ana I. Faustino-Rocha
    • 1
    • 2
    • 3
    • 7
    Email author
  • Adelina Gama
    • 1
    • 3
  • Paula A. Oliveira
    • 1
    • 2
  • Antonieta Alvarado
    • 2
    • 4
  • Maria J. Neuparth
    • 5
    • 6
  • Rita Ferreira
    • 7
  • Mário Ginja
    • 1
    • 2
  1. 1.Department of Veterinary Sciences, School of Agrarian and Veterinary SciencesUniversity of Trás-os-Montes and Alto Douro, UTADVila RealPortugal
  2. 2.Center for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB)University of Trás-os-Montes and Alto Douro, UTADVila RealPortugal
  3. 3.Animal and Veterinary Research Center (CECAV)University of Trás-os-Montes and Alto Douro, UTADVila RealPortugal
  4. 4.Área de Patología, Decanato de Ciencias VeterinariasUniversidad Centroccidental “Lisandro Alvarado”, UCLALaraVenezuela
  5. 5.Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS)CESPUGandraPortugal
  6. 6.Faculty of Sports, Research Centre in Physical Activity, Health and Leisure (CIAFEL)University of PortoPortoPortugal
  7. 7.Department of Chemistry, Organic Chemistry, Natural Products and Foodstuffs (QOPNA), Mass Spectrometry CenterUniversity of AveiroAveiroPortugal

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