Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis.
OBJECTIVE
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
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.
Ishikawa
Hitoshi
H
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences (NIRS), Chiba, Japan. hisikawa@med.gunma-u.ac.jp
Ohno
Tatsuya
T
Kato
Shingo
S
Wakatsuki
Masaru
M
Iwakawa
Mayumi
M
Ohta
Toshie
T
Imai
Takashi
T
Mitsuhashi
Norio
N
Noda
Shin-Ei
SE
Nakano
Takashi
T
Tsujii
Hirohiko
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy*
D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2