Induction of cytochrome P450 3A4 by docetaxel in peripheral mononuclear cells and its expression in lung cancer
Induction of cytochrome P450 3A4 by docetaxel in peripheral mononuclear cells and its expression in lung cancer
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DOI：
10.1007/s002800100291
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发表时间：
2001-07-01
影响因子：
3
通讯作者：
Kohno, N
中科院分区：
文献类型：
--
作者：
Fujitaka, K;Oguri, T;Kohno, N
最近的一些研究表明，细胞色素P450(CYP)家族在紫杉烷的代谢中起着重要的作用。然而。CYP基因在肿瘤和外周单核细胞(PMN)中的表达作用尚不清楚。因此，我们用逆转录聚合酶链式反应(RT-PCR)检测了16例未经治疗的肺癌患者中性粒细胞中CYP3A4和CYP2C基因的表达水平，以确定这两个基因的表达是否由多西紫杉醇(TXT)诱导。单独应用卡铂(CBDCA)后，细胞色素P450 3A4和细胞色素P450 2 C基因均未被诱导。单独给予TXT或TXT联合CBDCA可诱导细胞色素P3A4基因的表达。但细胞色素P450 2 C基因的表达未受影响。我们还利用RT-PCR技术检测了20例尸检标本(10例非小细胞肺癌及其相应的正常肺组织)中这两种基因的表达。肺癌组织中CYP2C基因的表达水平明显高于正常肺组织。而细胞色素P3A4基因表达水平无明显变化。这些结果表明，CYP3A4基因是由TXT诱导的，并且在细胞内TXT代谢中起重要作用。
Several recent studies have demonstrated that the cytochrome p450 (CYP) family plays an important role in the metabolism of taxanes. However. the role of CYP gene expression in tumors and peripheral mononuclear cells (PMN) is unknown. We therefore investigated the levels of CYP3A4 and CYP2C gene expression using reverse transcription polymerase chain reaction (RT-PCR) in PMN from 16 previously untreated lung cancer patients to determine whether the expression of the two genes is induced by docetaxel (TXT). Neither the CYP3A4 nor the CYP2C gene was induced after administration of carboplatin (CBDCA) alone. Expression of the CYP3A4 gene was induced by the administration of TXT alone or TXT and CBDCA. but expression of the CYP2C gene was unaffected. We also measured the expression of both genes using RT-PCR in 20 autopsy samples (ten non-small-cell lung cancers and their corresponding normal lung tissues) obtained from patients who had not received any chemotherapy during life. The level of CYP2C gene expression in samples of lung cancer was significantly higher than in normal lung tissue. but the level of CYP3A4 gene expression was not. These results suggest that the CYP3A4 gene is induced by TXT, and that it plays an important role in intracellular TXT metabolism.