Oxytocin mediates the beneficial effects of the exercise training on breast cancer

Exp Physiol. 2018 Feb 1;103(2):222-235. doi: 10.1113/EP086463. Epub 2017 Dec 25.

Abstract

What is the central question of this study? We hypothesized that potential anti-tumour effects of exercise training might be mediated by oxytocin and explored the underlying mechanisms in a mouse model of breast cancer. What is the main finding and its importance? Interval exercise training, by inducing oxytocin secretion, may reduce the activity of the PI3K/Akt and ERK pathways, and consequently, results in a smaller tumour volume in a mouse model of breast cancer. Exercise training can affect the growth of breast tumours. We hypothesized that exercise training might reduce breast tumour growth by inducing oxytocin (OT) secretion and its related signalling pathways, such as PI3K/Akt and ERK. Therefore, 56 BALB/c mice were equally divided into seven groups to study the effects of OT and atosiban (an oxytocin receptor antagonist) together with interval exercise training on mammary tumour growth, as well as tumour-related signalling pathways, including PI3K/Akt and ERK. Animal weight, OT plasma concentration, tumour weight and volume were measured at the end of the study. PI3K/Akt and ERK were evaluated by Western blot and qPCR assays. The results showed that OT plasma concentration was significantly increased in trained animals. The volume and weight of tumours were decreased significantly after both exercise training and OT administration. The expression of genes involved in tumour cell proliferation, such as PI3KR2, Akt and mTOR, was notably lower in the exercise-trained and OT-treated groups. Furthermore, the expression of genes involved in cell apoptosis, such as caspase-3 and Bax, was significantly increased in the tumour tissues. In addition, Western blot results showed that phosphorylated Akt and ERK were significantly decreased in the exercise training and OT groups compared with the tumour group. Interestingly, atosiban reversed these effects. These results indicated that interval exercise training, acting via OT secretion, may reduce PI3K/Akt and ERK axis activities, and consequently, decrease tumour volume and weight in a mouse model of breast cancer.

Keywords: Atosiban; breast cancer; exercise traininh; oxytocin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hormone Antagonists / pharmacology*
  • Mice, Inbred BALB C
  • Oxytocin / blood
  • Oxytocin / pharmacology*
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Physical Conditioning, Animal / methods
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Oxytocin / drug effects*
  • Receptors, Oxytocin / metabolism
  • TOR Serine-Threonine Kinases / drug effects
  • Vasotocin / analogs & derivatives*
  • Vasotocin / pharmacology

Substances

  • Hormone Antagonists
  • Receptors, Oxytocin
  • atosiban
  • Oxytocin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Vasotocin