Institute of Clinical Pharmacology, Zhengzhou University, Zhengzhou, Henan, 450001, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China.
Adv Sci (Weinh). 2023 Dec;10(35):e2303975. doi: 10.1002/advs.202303975. Epub 2023 Oct 24.
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.
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。
