Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis

Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1347-55. doi: 10.1016/j.ijrobp.2006.07.007. Epub 2006 Sep 18.

Abstract

Purpose: Cyclooxygenase-2 (COX-2) plays a pivotal role in regulation of radiation-induced apoptosis. The aim of this study was to analyze the relationship between COX-2 expression and postradiotherapy outcomes of patients with cervical cancer.

Methods and materials: Biopsy specimens from 47 consecutive patients who had undergone definitive radiotherapy alone or radiotherapy combined with chemotherapy between October 2002 and November 2004 were investigated.

Results: The COX-2 expression rate of the pretreatment samples was 46.1% +/- 21.0%, and the apoptotic index (AI) 1 week after start of radiotherapy was 2.1% +/- 0.9%. There was a significant negative correlation between the pretreatment COX-2 expression and the AI during radiotherapy (r = -0.52, p = 0.0002). Complete response rates were 59% for COX-2-positive patients compared with 80% for COX-2-negative patients (p = 0.12). The 2-year local control rate for COX-2-positive patients was 71.3%, whereas the corresponding rate for COX-2-negative patients was 96.0% (p = 0.06).

Conclusions: To the best of our knowledge, this is the first report to prove clinically that COX-2 can make cervical squamous cell carcinomas more refractory to radiotherapy by inhibition of radiation-induced apoptosis. Furthermore, expression of COX-2 may be a good indicator to predict local tumor control after radiotherapy. Although long-term results are ultimately needed, the combination therapy of radiotherapy with use of a COX-2 inhibitor could yield improved outcomes for patients with COX-2 expressing cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / radiotherapy*
  • Combined Modality Therapy
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • Neoplasm Proteins
  • Tumor Suppressor Protein p53
  • Cyclooxygenase 2