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

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.

Keywords: Cervical cancer, COX-2, Radiation therapy, Apoptosis, Local control