Effects of Ladder-Climbing Exercise on Mammary Cancer: Data from a Chemically Induced Rat Model

Abstract

Breast cancer remains a significant global health issue, affecting both humans and companion animals, particularly female dogs and cats, where mammary tumors are among the most common cancers. Strategies to minimize the impact of this disease on patients, pet owners, and veterinary medicine are essential. This study analyses the effects of resistance training on the development of chemically induced mammary cancer in female Wistar rats, divided into four groups: sedentary control (CTR), sedentary induced (CTR+N-methyl-N-nitrosourea (MNU)), exercised control (EX), and exercised induced (EX+MNU). The exercise protocol involved ladder climbing three times a week for 18 weeks with the load progressively increasing. At the study's end, blood and histopathological samples were collected and analyzed. Although tumor onset occurred two weeks earlier and incidence was slightly higher in the exercised group (EX+MNU) compared to the control group (CTR+MNU), the mortality rate was lower, and the malignancy was not as aggressive. No systemic inflammation was observed, as the levels of albumin, C-reactive protein (CRP), and interleukin 6 (IL-6) in the MNU groups remained similar to the controls. Exercise has been shown to promote overall health by increasing physical fitness, boosting immunological function, and improving metabolic health. These findings may offer valuable insights into the potential role of resistance training in managing mammary cancer in companion animals. However, further research is required to assess clinical applicability and to establish safe and effective exercise protocols for veterinary oncology.

Keywords: Wistar rats; breast cancer; physical activity; resistance training.

Figure 1

Experimental design. CTR: sedentary control group; CTR+MNU: sedentary induced group; EX: exercised control group and EX+MNU: exercised induced group.

Figure 2

Maximal carrying load capacity (MCL) per maximal strength test in both exercised groups (EX and EX+MNU) (mean ± S.D.). EX: exercised control group, and EX+MNU: exercised induced group.

Figure 3

Circulating levels of myostatin (A), C-reactive protein (CRP) (B), interleukin-6 (IL-6) (C), and vascular endothelial growth factor-A (VEGF-A) (D). Values are presented as mean ± S.D. in each group in optical density (OD). CTR: sedentary control group; CTR+MNU: sedentary induced group; EX: exercised control group and EX+MNU: exercised induced group. Statistically significant differences were not found (p > 0.05).

Figure 4

Effects of resistance training on the carcinogenic response of the mammary gland: cumulative number of mammary tumors in both MNU-induced groups (CTR+MNU and EX+MNU) throughout the experiment. CTR+MNU: sedentary induced group, and EX+MNU: exercised induced group.

Figure 5

H&E staining (A,B), and immunohistochemical staining for ERα (C,D), PR (E,F), and Ki-67 (G,H) in mammary tumors from the CTR+MNU (A,C,E,G) and EX+MNU (B,D,F,H) groups. Immunostaining was observed in the nuclei of epithelial cells. Statistically significant differences were found in the immunoexpression of ERα and PR between groups (p < 0.05). CTR+MNU: sedentary induced group, and EX+MNU: exercised induced group.

Figure 6

Immunoexpression of CD8 (A), intra-tumoral CD163 (B), extra-tumoral CD163 (C), and histochemical analysis of a double staining with toluidine blue and fuchsin orange G (D) in MNU-induced mammary tumors in both CTR+MNU and EX+MNU groups. Values are presented as mean ± S.D. in each group. CTR+MNU: sedentary induced group, and EX+MNU: exercised induced group. Statistically significant differences were not found (p > 0.05).

Figure 7

Immunoexpression of CD8 (A,B), CD163 (C,D), and double staining with toluidine blue and fuchsin orange G (E,F) in mammary tumors from the CTR+MNU (A,C,E) and EX+MNU (B,D,F) groups. Immunostaining was observed in the cytoplasm of epithelial and stromal cells (A–D). secretory granules of mast cells are stained in purple. Statistically significant differences were not found (p > 0.05). CTR+MNU: sedentary induced group, and EX+MNU: exercised induced group.