Nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes

Int J Radiat Oncol Biol Phys. 2005 Dec 1;63(5):1295-303. doi: 10.1016/j.ijrobp.2005.04.041. Epub 2005 Aug 15.

Abstract

Purpose: Recent studies have proposed that mucositis development is the same throughout the gastrointestinal tract (GIT), as it is formed from one structure embryologically. Radiation-induced oral mucositis studies have outlined the key involvement of nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) in its pathobiology. The purpose of this study was therefore to investigate the expression of NFkappaB and Cox-2 in the irradiated colorectum and to correlate these with the associated histopathologic changes.

Methods and materials: Colorectal tissues from 28 colorectal cancer patients treated with preoperative radiotherapy were analyzed for histopathologic changes using a variety of tissue staining methods. The expression of NFkappaB and Cox-2 in these tissues was investigated using immunohistochemistry. Changes in expression of these proteins were then correlated with the histopathologic changes.

Results: Radiation therapy caused injury to the normal colorectal tissue surrounding tumor site, particularly around the blood vessels. These changes were reflected in changes in NFkappaB and Cox-2 expression.

Conclusions: We conclude that different regions of the GIT, the colorectum, and oral cavity have similar underlying mechanisms of radiation-induced mucositis. Understanding these mechanisms will allow new approaches to be developed to specifically target steps in the evolution of alimentary mucositis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colon / metabolism
  • Colon / pathology
  • Colon / radiation effects*
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Goblet Cells / pathology
  • Goblet Cells / radiation effects
  • Humans
  • Male
  • Middle Aged
  • Mucositis / etiology
  • Mucositis / metabolism*
  • Mucositis / pathology
  • NF-kappa B / metabolism*
  • Radiation Injuries / metabolism*
  • Radiation Injuries / pathology
  • Rectal Neoplasms / metabolism
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy
  • Rectum / metabolism
  • Rectum / pathology
  • Rectum / radiation effects*

Substances

  • NF-kappa B
  • Cyclooxygenase 2