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Study on growth suppression and chemoprevention of lung cancer by cyclooxygenase 2 inhibitor

环氧合酶2抑制剂抑制肺癌生长及化学预防的研究

基本信息

批准号：
11670604
负责人：
HIDA Toyoaki
金额：
$ 2.3万
依托单位：
Aichi Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

We recently reported that an increased expression of COX-2 was frequently seen in a specific type of lung cancer, i.e., adenocarcinoma, and was possibly associated with its invasion and metastases. We have also shown the presence of a significant relationship between elevated COX-2 expression and shortened patient survival in a cohort of patients with stage I disease.We report here that COX-2 inhibitor could inhibit proliferation of non-small cell lung cancer (NSCLC) cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis even at clinically achievable low concentrations. Our observations also suggested that the state of COX-2 expression in NSCLC cells might influence their responsiveness to COX-2 inhibitors. Moreover, we found that COX-2 inhibitor, when used in combination at clinically achievable concentrations, reduced the IC_<50> values of various anticancer agents by up to 77%, although the levels of reduction varied considerably. In radiation sensitivity, COX-2 inhibitor was shown to have an additive effect on the efficacy of irradiation. Since our previous studies have indicated that significantly increased COX-2 expression is present in up to 70% of adenocarcinoma cases, the present findings are of great clinical interest and the recent development of next generation, highly selective COX-2 inhibitors should lead to even greater efficacy for the adjunct use with various anticancer agents in the treatment of high risk patients without compromising their quality of life.

我们最近报道了考克斯-2的表达增加在一种特定类型的肺癌中常见，即，腺癌，并可能与其浸润和转移。我们还表明，存在一个显着的关系升高考克斯-2的表达和缩短患者的生存期在一个队列中的患者与I期diseases.We报告在这里，考克斯-2抑制剂可以抑制增殖的非小细胞肺癌（NSCLC）细胞株在体外以剂量依赖的方式，部分通过诱导细胞凋亡，即使在临床上可达到的低浓度。我们的观察还表明，考克斯-2在NSCLC细胞中的表达状态可能影响其对考克斯-2抑制剂的反应性。此外，我们发现，考克斯-2抑制剂，当在临床上可达到的浓度组合使用时，降低<50>各种抗癌剂的IC_值高达77%，尽管降低的水平变化很大。在放射敏感性方面，考克斯-2抑制剂显示出对放射疗效的累加效应。由于我们以前的研究表明，显著增加的考克斯-2表达存在于高达70%的腺癌病例中，目前的发现具有很大的临床意义，并且下一代高选择性考克斯-2抑制剂的最新开发将导致与各种抗癌剂一起辅助使用在治疗高危患者中甚至更大的功效，而不损害他们的生活质量。