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

• Published in: International journal of radiation oncology, biology, physics Vol. 66; no. 5; pp. 1347 - 1355
• Main Authors: Ishikawa, Hitoshi, Ohno, Tatsuya, Kato, Shingo, Wakatsuki, Masaru, Iwakawa, Mayumi, Ohta, Toshie, Imai, Takashi, Mitsuhashi, Norio, Noda, Shin-ei, Nakano, Takashi, Tsujii, Hirohiko
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2006
• Subjects: Adult; Aged; Aged, 80 and over; APOPTOSIS; Apoptosis - physiology; BIOPSY; CARBON MONOXIDE; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - radiotherapy; CARCINOMAS; Cervical cancer; CHEMOTHERAPY; Combined Modality Therapy; CORRELATIONS; COX-2; Cyclooxygenase 2 - metabolism; Female; Humans; INHIBITION; Local control; Middle Aged; Neoplasm Proteins - metabolism; PATIENTS; Radiation therapy; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; REFRACTORIES; Treatment Outcome; Tumor Suppressor Protein p53 - metabolism; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - radiotherapy; Radiation therapy; COX-2; Local control; Cervical cancer; Apoptosis
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2006.07.007

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.