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一种新型细胞色素 P450 2E1 抑制剂 Q11 通过调节炎症微环境对肺癌有效。

A Novel Cytochrome P450 2E1 Inhibitor Q11 Is Effective on Lung Cancer via Regulation of the Inflammatory Microenvironment.

机构信息

Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, 450001, China.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China.

出版信息

Adv Sci (Weinh). 2023 Dec;10(35):e2303975. doi: 10.1002/advs.202303975. Epub 2023 Oct 24.

DOI:10.1002/advs.202303975
PMID:37875398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10724398/
Abstract

Lung cancer is the leading cause of death among all cancers. A persistent chronic inflammatory microenvironment is highly correlated with lung cancer. However, there are no anti-inflammatory agents effective against lung cancer. Cytochrome P450 2E1 (CYP2E1) plays an important role in the inflammatory response. Here, it is found that CYP2E1 is significantly higher in the peritumoral tissue of non-small cell lung cancer (NSCLC) patients and lung tumor growth is significantly impeded in Cyp2e1 mice. The novel CYP2E1 inhibitor Q11, 1-(4-methyl-5-thialzolyl) ethenone, is effective in the treatment of lung cancer in mice, which can inhibit cancer cells by changing macrophage polarization rather than directly act on the cancer cells. It is also clarify that the benefit of Q11 may associated with the IL-6/STAT3 and MAPK/ERK pathways. The data demonstrate that CYP2E1 may be a novel inflammatory target and that Q11 is effective on lung cancer by regulation of the inflammatory microenvironment. These findings provide a molecular basis for targeting CYP2E1 and illustrate the potential druggability of the CYP2E1 inhibitor Q11.

摘要

肺癌是所有癌症中导致死亡的主要原因。持续的慢性炎症微环境与肺癌高度相关。然而，目前还没有针对肺癌有效的抗炎药物。细胞色素 P450 2E1（CYP2E1）在炎症反应中起着重要作用。研究发现，非小细胞肺癌（NSCLC）患者肿瘤周围组织中的 CYP2E1 明显升高，Cyp2e1 小鼠的肺肿瘤生长明显受到抑制。新型 CYP2E1 抑制剂 Q11，1-(4-甲基-5-噻唑基)乙酮，可有效抑制小鼠肺癌，通过改变巨噬细胞极化而非直接作用于癌细胞来抑制癌细胞。研究还阐明，Q11 的益处可能与 IL-6/STAT3 和 MAPK/ERK 通路有关。数据表明，CYP2E1 可能是一个新的炎症靶点，Q11 通过调节炎症微环境对肺癌有效。这些发现为靶向 CYP2E1 提供了分子基础，并说明了 CYP2E1 抑制剂 Q11 的潜在成药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/c1d0e338858a/ADVS-10-2303975-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/c5f81a6e0505/ADVS-10-2303975-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/135f05e5a3bf/ADVS-10-2303975-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/7715b52da65a/ADVS-10-2303975-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/62a5db7c92ef/ADVS-10-2303975-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/089304997bc1/ADVS-10-2303975-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/66b860118495/ADVS-10-2303975-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/c1d0e338858a/ADVS-10-2303975-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/c5f81a6e0505/ADVS-10-2303975-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/135f05e5a3bf/ADVS-10-2303975-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/7715b52da65a/ADVS-10-2303975-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/62a5db7c92ef/ADVS-10-2303975-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/089304997bc1/ADVS-10-2303975-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/66b860118495/ADVS-10-2303975-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0f/10724398/c1d0e338858a/ADVS-10-2303975-g005.jpg

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引用本文的文献

[1]
Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.

Precis Clin Med. 2025-2-22

[2]
Q11, a CYP2E1 inhibitor, exerts anti-hepatocellular carcinoma effect by inhibiting M2 macrophage polarization.

Cancer Immunol Immunother. 2024-12-30

[3]
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Bioinformatics. 2024-11-1

[4]
Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.

Biomedicines. 2024-7-5

[5]
Role of the gut microbiota in tumorigenesis and treatment.

Theranostics. 2024-3-17

本文引用的文献

[1]
The CYP2E1 inhibitor Q11 ameliorates LPS-induced sepsis in mice by suppressing oxidative stress and NLRP3 activation.

Biochem Pharmacol. 2023-8

[2]
Identification of Cytochrome P450 2E1 as a Novel Target in Glioma and Development of Its Inhibitor as an Anti-Tumor Agent.

Adv Sci (Weinh). 2023-8

[3]
The Bidirectional Relationship between Pulmonary Tuberculosis and Lung Cancer.

Int J Environ Res Public Health. 2023-1-10

[4]
CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling.

J Transl Med. 2022-5-4

[5]
The proteomic characterization of the peritumor microenvironment in human hepatocellular carcinoma.

Oncogene. 2022-4

[6]
Tumor-associated macrophages in lung carcinoma: From mechanism to therapy.

Pathol Res Pract. 2022-1

[7]
Links between Infections, Lung Cancer, and the Immune System.

Int J Mol Sci. 2021-8-30

[8]
Inflammation and tumor progression: signaling pathways and targeted intervention.

Signal Transduct Target Ther. 2021-7-12

[9]
Macrophage Polarization States in the Tumor Microenvironment.

Int J Mol Sci. 2021-6-29

[10]
The Role of Tumor Inflammatory Microenvironment in Lung Cancer.

Front Pharmacol. 2021-5-17

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