The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer

Can J Physiol Pharmacol. 2020 Mar;98(3):147-155. doi: 10.1139/cjpp-2019-0329. Epub 2019 Oct 15.

Abstract

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program (P < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.

Keywords: ACF; COX-2; PCNA; apoptose; apoptosis; cancer colorectal; colorectal cancer; dimethylhydrazine; diméthylhydrazine; exercice physique; exercise; foyers de cryptes aberrantes.

MeSH terms

  • 1,2-Dimethylhydrazine / toxicity*
  • Aberrant Crypt Foci / chemically induced
  • Aberrant Crypt Foci / metabolism
  • Aberrant Crypt Foci / pathology
  • Aberrant Crypt Foci / therapy*
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinogens / toxicity
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism*
  • Male
  • Physical Conditioning, Animal*
  • Rats
  • Rats, Wistar

Substances

  • Apoptosis Regulatory Proteins
  • Carcinogens
  • Inflammation Mediators
  • 1,2-Dimethylhydrazine