DEC1 negatively regulates CYP2B6 expression by binding to the CYP2B6 promoter region ascribed to IL-6-induced downregulation of CYP2B6 expression in HeLa cells

Abstract

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.