Effects of lifelong exercise training on mammary tumorigenesis induced by MNU in female Sprague–Dawley rats
- 419 Downloads
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.
KeywordsEstradiol Estrogen receptors Exercise Mammary tumors MNU
Hematoxylin and eosin
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.
All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 1.Harvie M, Howell A, Evans D. Can diet and lifestyle prevent breast cancer: what is the evidence? ASCO. 2015;35:66–73.Google Scholar
- 10.Kuiper GGJM, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997;138:863–70.Google Scholar
- 24.Forbes D, Blom H, Kostomitsopulos N, Moore G, Perretta G. Euroguide: on the accommodation and care of animals used for experimental and other scientific purposes. London: FELASA; 2007.Google Scholar
- 35.Zeleniuch-Jacquotte A, Toniolo P, Levitz M, et al. Endogenous estrogens and risk of breast cancer by estrogen receptor status: a prospective study in postmenopausal women. Cancer Epidemiol Biomark. 1995;4:857–60.Google Scholar
- 37.Faustino-Rocha AI, Silva A, Gabriel J, Gil da Costa RM, Moutinho M, Oliveira PA,Gama A, Ferreira R, Ginja M. Long-term exercise training as a modulator of mammary cancer cascularization. Biomed Pharmacother. 2016;(Accepted).Google Scholar