Effect of Physical Training on the Levels of Sex Hormones and the Expression of Their Receptors in Rats With Induced Mammary Cancer in Secondary Prevention Model – Preliminary Study

Abstract

Background/Aim: Breast cancer is the most common malignant tumor among women worldwide. In previous work, we presented results of physical activity in primary prevention in a model of induced mammary gland cancer. In the present study, we assessed the influence of physical activity on sex hormone levels (estradiol and progesterone) and the expression of their receptors (ER, PR), as well as the level of apoptosis of tumor cells in secondary prevention. Materials and Methods: Fifty 1-month-old female Sprague-Dawley rats received intraperitoneal injection of 180 mg/kg body weight of N-methyl-N-nitrosourea (MNU) for tumor induction. Three months after the administration of MNU, rats were divided into four groups: low-intensity, moderate-intensity, and high-intensity physical training groups (combined as PT) and a sedentary control (SC) group. Physical training was conducted 5 days per week with a threeposition treadmill according to a precisely described protocol. The entire training was completed by 32 rats from which tissue and blood were collected for further analysis. Immunohistochemistry for ER and PR expression, terminal deoxynucleotidyl transferase dUTP nick-end labeling method for detection of apoptosis, and enzyme-linked fluorescent assay for detection of plasma hormone levels (estradiol and progesterone) were performed. Statistical analysis used p<0.05 as the significance level. Results: Significantly stronger expression of ER and PR was found in the SC in comparison to the PT group (p=0.035 and p=0.036, respectively). No statistically significant differences were found in estradiol or progesterone concentrations between SC and PT groups. Apoptosis was non-significantly increased in the PT group in comparison with the SC group. Stronger apoptosis in the PT group correlated positively with the level of training intensity (r=0.35, p=0.05). Conclusion: Physical training may reduce ER and PR expression in breast cancer cells, and reduce cell sensitivity to pro-proliferative and antiapoptotic effects of estrogens, ultimately leading to apoptosis. Breast cancer is the most common malignant tumor among women worldwide (30%), being the second leading cause of cancer-related death in the United States and in Europe (14%) (1). Nearly 20% of women worldwide are diagnosed at 30-49 years of age and over 40% of women aged 65 years or over (2). Estrogens play an important role in the pathogenesis of breast cancer. Estradiol stimulates cell proliferation and differentiation by estrogen receptor (ER). Many reports indicate the relationship between exposure to estrogens and 495 This article is freely accessible online.

Effect of Exercise on Breast Cancer: A Systematic Review and Meta-analysis of Animal Experiments

“…Among the included studies, 21 studies ( Steiner et al, 2013 ; Shalamzari et al, 2014 ; Alvarado et al, 2017 ; Alizadeh et al, 2018 ; Murphy et al, 2011 ; Aveseh et al, 2015 ; Leila et al, 2015 ; Malicka et al, 2015 ; Isanejad et al, 2016 ; Cui, 2017 ; Nasiri et al, 2017 ; Lyv Di et al, 2021 ; Qi et al, 2013 ; Siewierska et al, 2018 ; Siewierska et al, 2020 ; Wen et al, 2010 ; Gholamian et al, 2020 ; Vulczak et al, 2020 ; Wennerberg et al, 2020 ) reported that exercise could decrease the tumor volume, 1 ( Faustino-Rocha et al, 2016 ) reported negative effects of exercise, and 2 ( Smeda et al, 2017 ; Garritson et al, 2019 ) reported that exercise had no effect on the tumor volume.…”

Estrogen-Receptor-Positive Breast Cancer in Postmenopausal Women: The Role of Body Composition and Physical Exercise

“…To date, it is still a challenge to estimate the magnitude of the clinical impact of PA on the observed levels of sex hormones, since there are no absolute cut-off values defined that correspond with a certain change in future BC risk and disease progression. However, besides an important effect on circulating sex hormone levels, it should also be considered that different studies on pre-clinical BC animal models demonstrate an important effect of PA to increase the ERβ/ERα ratio, as well as an increase in mammary gland cell apoptosis [ 41 , 176 , 177 ].…”

“…To date, few studies performed in rat models following physical training analyzed the expression of ER in BC cells. In these studies, authors demonstrated an effect of PA in increasing the ratio of ERβ/ERα, and a reduction in the sensitivity of BC cells to the pro-proliferative and antiapoptotic effects of estrogen, leading to apoptotic cell death [ 41 ].…”