Liu Di, Huang Ye, Shang You
Department of Anesthesiology, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Guta District, Jinzhou, 121001, Liaoning Province, China.
Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, Liaoning Province, China.
Mol Biotechnol. 2025 Mar;67(3):1054-1064. doi: 10.1007/s12033-024-01104-x. Epub 2024 Mar 12.
Sufentanil is a common opioid anesthetic agent, which exerts anti-cancer properties in several cancer types. However, its action mechanisms in non-small cell lung cancer (NSCLC) are unclear. Therefore, the present study investigated the pharmacological effect of sufentanil on miRNAs in NSCLC treatment. In this study, after treatment with sufentanil, the proliferation, migration, invasion and apoptosis of A549 and H1299 NSCLC cell lines were measured by cell counting kit-8 (CCK-8) assay, colony formation assay, transwell assays and flow cytometry. Quantitative real time polymerase chain reaction (qRT-PCR) was utilized to detect the expression of miR-186-5p and high mobility group box-1 (HMGB1), and their interaction was analyzed using luciferase reporter assay. The proteins of HMGB1, and apoptosis- and Wnt/β-catenin pathway-related factors were detected by western blot. It was demonstrated that sufentanil significantly upregulated miR‑186‑5p to restrict NSCLC cell proliferation, migration, invasion, and boost apoptosis in vitro. Mechanically, miR-186-5p interacted with HMGB1 and negatively regulated HMGB1 in NSCLC cells. Furthermore, rescue assay showed that sufentanil exerted antitumor activities by upregulating miR-186-5p, which targeted HMGB1 and restrained Wnt/β-catenin signal pathway in NSCLC cells. In conclusion, these results suggested that sufentanil disrupts the oncogenicity of NSCLC cells by regulating miR-186-5p/HMGB1/β-catenin axis, providing a promising implication for the anti-oncogenic effect of sufentanil.
舒芬太尼是一种常见的阿片类麻醉剂，在多种癌症类型中具有抗癌特性。然而，其在非小细胞肺癌（NSCLC）中的作用机制尚不清楚。因此，本研究探讨了舒芬太尼在NSCLC治疗中对微小RNA（miRNA）的药理作用。在本研究中，用舒芬太尼处理后，通过细胞计数试剂盒-8（CCK-8）检测、集落形成检测、Transwell检测和流式细胞术检测A549和H1299 NSCLC细胞系的增殖、迁移、侵袭和凋亡。利用定量实时聚合酶链反应（qRT-PCR）检测miR-186-5p和高迁移率族蛋白B1（HMGB1）的表达，并使用荧光素酶报告基因检测分析它们之间的相互作用。通过蛋白质印迹法检测HMGB1以及凋亡和Wnt/β-连环蛋白通路相关因子的蛋白质。结果表明，舒芬太尼显著上调miR-186-5p，以限制NSCLC细胞在体外的增殖、迁移、侵袭并促进凋亡。机制上，miR-186-5p与HMGB1相互作用并在NSCLC细胞中负调控HMGB1。此外，挽救实验表明，舒芬太尼通过上调靶向HMGB1并抑制NSCLC细胞中Wnt/β-连环蛋白信号通路的miR-186-5p发挥抗肿瘤活性。总之，这些结果表明舒芬太尼通过调节miR-186-5p/HMGB1/β-连环蛋白轴破坏NSCLC细胞的致癌性，为舒芬太尼的抗癌作用提供了有前景的启示。
