Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Xenobiotica. 2021 Dec;51(12):1343-1351. doi: 10.1080/00498254.2021.2004335. Epub 2021 Nov 28.
The cytochrome P450 superfamily (CYPs) is a group of metabolic enzymes involved in drug biotransformation/metabolism. It is the most important drug metabolic enzyme; however, its mechanism of action remains unclear.We investigated the expression of CYP2B6 in HeLa cells induced by interleukin-6 (IL-6) and explored the relationship between differentially expressed chondrocytes 1 (DEC1) and CYP2B6 via luciferase reporter, chromatin immunoprecipitation (ChIP) and ELISA assays.We observed the expression of CYP2B6 in HeLa cells exhibited a time-dependent decrease under the effect of IL-6, and the expression of CYP2B6 down-regulated by IL-6was negatively correlated with DEC1. After overexpression or knockdown of DEC1 in HeLa cells, the expression of CYP2B6 decreased or increased. The luciferase reporter assay and ChIP assay confirmed that DEC1 inhibited the expression of CYP2B6 by binding to the CYP2B6 promoter. ELISA results showed that high expression of DEC1 or low expression of CYP2B6 can promote the secretion of IL-6 in HeLa cells, and the secreted IL-6 can continually downregulate the expression of CYP2B6 in HeLa cells.Our results indicate that DEC1/CYP2B6 pathway in the inflammatory environment of tumours, and this provides a small amount of theoretical basis for the study of genes encoding drug-metabolising enzymes.
细胞色素 P450 超家族（CYPs）是一组参与药物生物转化/代谢的代谢酶。它是最重要的药物代谢酶；然而，其作用机制仍不清楚。我们研究了白细胞介素-6（IL-6）诱导的 HeLa 细胞中 CYP2B6 的表达，并通过荧光素酶报告、染色质免疫沉淀（ChIP）和 ELISA 分析探讨了差异表达的软骨细胞 1（DEC1）和 CYP2B6 之间的关系。我们观察到在 IL-6 的作用下，HeLa 细胞中 CYP2B6 的表达呈时间依赖性下降，而 IL-6 下调的 CYP2B6 表达与 DEC1 呈负相关。在 HeLa 细胞中转染 DEC1 过表达或敲低后，CYP2B6 的表达降低或升高。荧光素酶报告和 ChIP 分析证实 DEC1 通过与 CYP2B6 启动子结合抑制 CYP2B6 的表达。ELISA 结果表明，高表达 DEC1 或低表达 CYP2B6 可促进 HeLa 细胞中 IL-6 的分泌，而分泌的 IL-6 可不断下调 HeLa 细胞中 CYP2B6 的表达。我们的结果表明 DEC1/CYP2B6 通路在肿瘤炎症环境中，这为研究编码药物代谢酶的基因提供了少量的理论依据。
