Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis
Cyclooxygenase-2 impairs treatment effects of radiotherapy for cervical cancer by inhibition of radiation-induced apoptosis
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DOI：
10.1016/j.ijrobp.2006.07.007
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发表时间：
2006-12-01
影响因子：
7
通讯作者：
Tsujii, Hirohiko
中科院分区：
文献类型：
--
作者：
Ishikawa, Hitoshi;Ohno, Tatsuya;Tsujii, Hirohiko
目的：环氧合酶-2（考克斯-2）在辐射诱导的细胞凋亡中起重要调节作用。本研究的目的是分析考克斯-2表达与宫颈癌患者放疗后预后的关系。方法和材料：对2002年10月至2004年11月间连续47例单纯放疗或放疗联合化疗的宫颈癌患者的活检标本进行研究。放疗前标本的考克斯-2表达率为46.1% ± 21.0%，放疗开始后1周的凋亡指数（AI）为2.1% ± 0.9%。放疗前考克斯-2表达与放疗期间AI呈显著负相关（r =-0.52，p = 0.0002）。考克斯-2阳性患者的完全缓解率为59%，而考克斯-2阴性患者的完全缓解率为80%（p = 0.12）。考克斯-2阳性患者2年局部控制率为71.3%，而考克斯-2阴性患者2年局部控制率为96.0%（p = 0.06）。结论：考克斯-2通过抑制放射诱导的细胞凋亡，使宫颈鳞癌对放射治疗更加难治。考克斯-2的表达可能是预测放疗后局部肿瘤控制的良好指标。尽管最终需要长期结果，但放疗与使用考克斯-2抑制剂的联合治疗可改善表达考克斯-2的宫颈癌患者的结局。(c)2006年爱思唯尔公司
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. (c) 2006 Elsevier Inc.