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细胞色素 P450 1B1 在非小细胞肺癌中的表达降低。

Decreased expression of cytochrome p450 1B1 in non-small cell lung cancer.

机构信息

Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, Święcickiego 6 Street, 60-781 Poznan, Poland.

Department of Thoracic Surgery, Poznan University of Medical Sciences, Szamarzewskiego 62 Street, 60-569 Poznan, Poland.

出版信息

Biomed Pharmacother. 2017 Nov;95:339-345. doi: 10.1016/j.biopha.2017.08.056. Epub 2017 Sep 12.

DOI:10.1016/j.biopha.2017.08.056
PMID:28858732
Abstract

Recent studies have associated oestrogen metabolism and cigarette smoking with their carcinogenic impact on the lungs. Compounds commonly found in tobacco smoke induce the activity of CYP1B1, the enzyme responsible for the synthesis of catecholic derivatives of oestrogens. During their redox transformations, these structures can release large amounts of reactive oxygen species or can form DNA adducts, which lead to the decomposition of genetic material. This process may illustrate the synergistic effect of oestrogenic activity and tobacco combustion on oestrogen-dependant lung cancer development. There is considerable evidence suggesting that the level of oestrogen in lung tumours is elevated. Therefore, by using reverse transcription, real-time PCR and Western Blot analysis, we evaluated the CYP1B1 status in tissues from 76 patients diagnosed with non-small cell lung cancer (NSCLC) to confirm whether potential overexpression of CYP1B1 may impact lung cancerogenesis induced by oestrogens. We found significantly lower levels of CYP1B1 transcripts (p=0.00001) and proteins (p=0.000085) in lung tumour material compared to corresponding, histopathologically unchanged tissues. We also analysed the association of CYP1B1 expression with gender, age and clinicopathological data of NSCLC patients. We observed lower amounts of CYP1B1 occurring in the middle stages of LC, regardless of gender, age or histological type of lung cancer.

摘要

最近的研究表明,雌激素代谢和吸烟与其对肺部的致癌作用有关。烟草烟雾中常见的化合物会诱导 CYP1B1 的活性,CYP1B1 是合成雌激素儿茶酚衍生物的酶。在它们的氧化还原转化过程中,这些结构可以释放大量的活性氧物质,或者可以形成 DNA 加合物,导致遗传物质的分解。这个过程可能说明了雌激素活性和烟草燃烧对雌激素依赖性肺癌发展的协同作用。有相当多的证据表明,肺癌组织中的雌激素水平升高。因此,我们通过使用逆转录、实时 PCR 和 Western Blot 分析,评估了 76 名非小细胞肺癌(NSCLC)患者组织中的 CYP1B1 状态,以确认 CYP1B1 的潜在过表达是否会影响雌激素诱导的肺癌发生。我们发现,与相应的组织学不变的组织相比,肺癌组织中的 CYP1B1 转录本(p=0.00001)和蛋白(p=0.000085)水平显著降低。我们还分析了 CYP1B1 表达与 NSCLC 患者性别、年龄和临床病理数据的相关性。我们观察到,无论性别、年龄或肺癌的组织学类型如何,在 LC 的中期,CYP1B1 的含量都较低。

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