Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma

FEBS Open Bio

Zhao‐huan Lou¹  Ai‐song Zhu²  Chu‐yun Xu²  Tao Jiang²  Dan‐qian Yang²  Chu‐qi Yang²  Guang‐ji Zhang² 

[1] College of Pharmaceutical Science Zhejiang Chinese Medical University Hangzhou China;School of Basic Medical Sciences Zhejiang Chinese Medical University Hangzhou China;

关键词: arachidonic acid;    cytochrome P450;    hepatocellular carcinoma;    macrophage polarization;    tanshinone IIA;   

DOI  :  10.1002/2211-5463.13089

来源: DOAJ

【 摘 要 】

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

【 授权许可】

Unknown