Effects of cigarette smoking and restraint stress on human colon tumor growth in mice

Digestion. 2009;80(4):209-14. doi: 10.1159/000231898. Epub 2009 Sep 17.

Abstract

Background: Cigarette smoking is a risk factor for colon cancer. Studies suggest that stress increases the incidence and promotes the development of cancers. Cigarette smoking and stress are closely associated, as people often smoke under stressful conditions and both of them can activate the adrenergic nervous system.

Aims: To investigate the effects of cigarette smoking and restraint stress on colon cancer growth and the possible underlying mechanisms in these pathological processes.

Methods: Nude mice bearing a HT-29 human colon cancer xenograft were either exposed to cigarette smoke and/or restraint stress. Cotinine and epinephrine levels in plasma of nude mice were measured by enzyme immunoassays. Expression of cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) in tumor tissues were detected by Western blot. Prostaglandin E(2) (PGE(2)) concentrations were determined by enzyme immunoassay.

Results: 4% cigarette smoking together with restraint stress 1 h daily for 33 days promoted tumor growth in nude mice. This was accompanied by the increase of plasma levels of cotinine and epinephrine in these animals. They also enhanced the COX-2, Bcl-2 expressions and PGE(2) levels in tumor tissues.

Conclusion: These findings are important in understanding the pathogenesis of colon cancer, particularly related to cigarette smoking and stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / etiology*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / psychology
  • Animals
  • Colonic Neoplasms / etiology*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / psychology
  • Cotinine / blood
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Epinephrine / blood
  • Female
  • HT29 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Smoking / adverse effects*
  • Stress, Psychological / complications*
  • Transplantation, Heterologous

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Cyclooxygenase 2
  • Cotinine
  • Dinoprostone
  • Epinephrine