Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines.
Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines.
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发表时间：
2000-05
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通讯作者：
T. Hida;K. Kozaki;Hideki Muramatsu;A. Masuda;S. Shimizu;T. Mitsudomi;T. Sugiura;M. Ogawa;Takashi Takahashi
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作者：
T. Hida;K. Kozaki;Hideki Muramatsu;A. Masuda;S. Shimizu;T. Mitsudomi;T. Sugiura;M. Ogawa;Takashi Takahashi
近年来，人口中老年人口数量的增加和肺癌发病率的增加这两个人口现象的结合，使得开发毒性较小的治疗方法来治疗无法手术的老年肺癌患者变得势在必行。我们的研究表明，环氧合酶(COX)-2抑制剂尼美舒利在体外可以剂量依赖的方式抑制非小细胞肺癌细胞系的增殖，部分是通过诱导细胞凋亡，即使在临床上可以达到的低浓度。我们的观察还表明，非小细胞肺癌对COX-2抑制剂的反应性不需要野生型P53的存在，但可能受到COX-2表达程度的影响。此外，我们发现，当尼美舒利以临床可达到的浓度联合使用时，各种抗癌药物的IC50值降低了77%，尽管降低的程度差别很大。由于我们之前的研究表明，在高达70%的腺癌病例中，COX-2的表达显著增加，因此目前的研究结果具有很大的临床意义。随着新一代、高选择性COX-2抑制剂的最新开发，它们有望在不影响生活质量的情况下，作为各种抗癌药物的辅助剂，在治疗高危患者方面取得更大的疗效。
In recent years, a combination of two demographic phenomena, an increase in the number of older people in the population and an increase in the incidence of lung cancer with age, has made it mandatory to develop therapeutic modalities with less toxicity for the treatment of inoperable elderly patients with lung cancer. Our study shows that a cyclooxygenase (COX)-2 inhibitor, nimesulide, can inhibit proliferation of non-small cell lung cancer cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis even at clinically achievable low concentrations. Our observations also suggest that the responsiveness of non-small cell lung cancer to COX-2 inhibitors does not require the presence of wild-type p53, but may be influenced by the degree of COX-2 expression. In addition, we found that nimesulide, when used in combination at clinically achievable concentrations, reduced the IC50 values of various anticancer agents by up to 77%, although the level of reduction varied considerably. Because our previous studies have indicated a significantly increased COX-2 expression in up to 70% of adenocarcinoma cases, the present findings are of great clinical interest. In conjunction with the recent development of next generation, highly selective COX-2 inhibitors, they can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer agents for the treatment of high-risk patients without compromising their quality of life.