Oyama Tsunehiro, Sugio Kenji, Isse Toyohi, Matsumoto Akiko, Nose Naohiro, Uramoto Hidetaka, Nozoe Tadahiro, Morita Masaru, Kagawa Norio, Osaki Toshihiro, Muto Manabu, Yasumoto Kosei, Kawamoto Toshihiro
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
Front Biosci. 2008 May 1;13:5787-93. doi: 10.2741/3116.
Lung cancer accounts for most of cancer-related deaths in both men and women. Lung cancer is also associated with cigarette smoking that exposes the individual to carcinogenic chemicals. Normally, CYP enzymes (cytochrome P450s) metabolize carcinogens to inactive derivatives, however, occasionally the action of CYP enzymes leads to development of more potent carcinogens. In addition to the metabolism of carcinogenic compounds, CYP enzymes are also involved in the activation and/or inactivation of agents, which are used in the treatment of lung cancer. Therefore, the local level of CYP enzymes in lung cancer and surrounding tissues could be an important determinant in the efficacy of anticancer drugs. Furthermore, the expression of CYP19 (aromatase), estrogen synthesis P450, was found in more than 80 percent of non-small cell lung cancers. Lung cancer was also found to frequently express CYP24A1 that converts 1 alpha, 25-dihydroxyvitamin D3 to its inactive 24-hydroxylated derivatives. The understanding of the local expression of CYP enzymes in tumor tissues is important in the development of better treatment for lung cancer and a standardized treatment, tailor-made, for individual patients.
肺癌是男性和女性癌症相关死亡的主要原因。肺癌还与吸烟有关,吸烟会使个体接触致癌化学物质。正常情况下,细胞色素P450(CYP)酶将致癌物代谢为无活性的衍生物,然而,CYP酶的作用偶尔也会导致产生更强效的致癌物。除了代谢致癌化合物外,CYP酶还参与肺癌治疗药物的激活和/或失活。因此,肺癌及周围组织中CYP酶的局部水平可能是抗癌药物疗效的重要决定因素。此外,在超过80%的非小细胞肺癌中发现了CYP19(芳香化酶)的表达,它是雌激素合成的P450。还发现肺癌经常表达CYP24A1,该酶将1α,25-二羟基维生素D3转化为其无活性的24-羟基化衍生物。了解肿瘤组织中CYP酶的局部表达对于开发更好的肺癌治疗方法以及为个体患者量身定制标准化治疗方法具有重要意义。