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

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.

Long-term exercise training as a modulator of mammary cancer vascularization

“…However, in both groups, the number of malignant lesions was higher than the number of benign ones. Papillary carcinoma was the most frequently identified histological pattern, in accordance with previous findings [38,43]. It worth to note that exercised animals did not develop any invasive comedocarcinoma, the most aggressive lesions diagnosed in sedentary animals, further suggesting that exercise training played a protective effect.…”

A Contrast‐Enhanced Ultrasonographic Study About the Impact of Long‐term Exercise Training on Mammary Tumor Vascularization

“…The practice of exercise training has been associated with a decreased risk of development of several types of cancer: namely, breast, endometrial, prostate, colon, and lung cancer . It was previously observed by our research team that long‐term exercise training reduced the number and malignancy of tumors and increased estrogen receptor expression in mammary tumors that were chemically induced in female rats . This work intended to evaluate the impact of long‐term exercise training on the vascularization of mammary tumors chemically induced in a rat model by US using a second‐generation contrast agent.…”

Impact of Physical Training on Sex Hormones and Their Receptors During N-Methyl-N-nitrosoureainduced Carcinogenesis in Rats

“…Similar observations were disclosed by others (25,26,31), whereas Erich et al (32) and PellerinMassocotte et al were explaining that rodents require high intensity PT to induce hormonal changes, especially related to sex hormones (33). Contrary to the general assumption that estrogen level decreases under the influence of PT, there is evidence of a significant increase of 17-β estradiol in rats undergoing long-term PT, most of all obtained by FaustinoRocha et al in the longest exercise training protocol (35-week) on mammary tumorigenesis ever performed (34).…”