Murray G I, Taylor M C, Burke M D, Melvin W T
Department of Pathology, University of Aberdeen, Foresterhill, UK.
Br J Cancer. 1998 Apr;77(7):1040-4. doi: 10.1038/bjc.1998.173.
The cytochromes P450 have a central role in the oxidative activation and detoxification of a wide range of xenobiotics, including many carcinogens and several anti-cancer drugs. Thus the cytochrome P450 enzyme system has important roles in both tumour development and influencing the response of tumours to chemotherapy. Stomach cancer is one of the commonest tumours of the alimentary tract and environmental factors, including dietary factors, have been implicated in the development of this tumour. This type of tumour has a poor prognosis and responds poorly to current therapies. In this study, the presence and cellular localization of several major forms of P450, CYP1A, CYP2E1 and CYP3A have been investigated in stomach cancer and compared with their expression in normal stomach. There was enhanced expression of CYP1A and CYP3A in stomach cancer with CYP1A present in 51% and CYP3A present in 28% of cases. In contrast, no P450 was identified in normal stomach. The presence of CYP1A and CYP3A in stomach cancer provides further evidence for the enhanced expression of specific forms of cytochrome P450 in tumours and may be important therapeutically for the development of anti-cancer drugs that are activated by these forms of P450.
细胞色素P450在多种外源性物质（包括许多致癌物和几种抗癌药物）的氧化活化和解毒过程中发挥着核心作用。因此，细胞色素P450酶系统在肿瘤发展以及影响肿瘤对化疗的反应方面都具有重要作用。胃癌是消化道最常见的肿瘤之一，环境因素（包括饮食因素）与这种肿瘤的发生有关。这种类型的肿瘤预后较差，对当前治疗反应不佳。在本研究中，已对几种主要形式的P450（CYP1A、CYP2E1和CYP3A）在胃癌中的存在情况和细胞定位进行了研究，并与它们在正常胃中的表达进行了比较。胃癌中CYP1A和CYP3A表达增强，51%的病例中存在CYP1A，28%的病例中存在CYP3A。相比之下，在正常胃中未鉴定出P450。胃癌中CYP1A和CYP3A的存在为肿瘤中细胞色素P450特定形式的表达增强提供了进一步证据，并且对于由这些形式的P450激活的抗癌药物的开发可能具有重要的治疗意义。
