Jiao Jinghua, Tang Yifang, Ye Lu, Yang Yaru, Liu Zhenghua
Department of Anesthesiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.
Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, China.
Sci Rep. 2025 May 14;15(1):16796. doi: 10.1038/s41598-025-01625-8.
Anesthesia and perioperative management significantly influence long-term outcomes in patients with early and intermediate stage cancer. Midazolam, a commonly used benzodiazepine anesthetic, has shown potential anti-tumor effects. This study aimed to explore the anti-tumor properties of midazolam in non-small cell lung cancer (NSCLC). The anti-tumor effects of midazolam on A549 and H1650 NSCLC cell lines were assessed using CCK-8 assays, colony-forming assays, and the Annexin V-fluorescein isothiocyanate Apoptosis Detection Kit I. Additionally, Transwell assays were conducted in vitro, and subcutaneous tumor models in nude mice were established to assess the anti-tumor effects in vivo. The interaction within the lncRNA XLOC_010706/miR-520d-5p/STAT3 axis was confirmed through dual-luciferase reporter assays, RT-qPCR, and Western blotting. Midazolam significantly inhibited cell proliferation and invasion while inducing apoptosis in A549 and H1650 cells, both in vitro and in vivo, by promoting autophagy (P<0.05). It also down-regulated the expression of lncRNA XLOC_010706 in the tumor microenvironment (P<0.05). Within the signaling pathway, lncRNA XLOC_010706 functioned as a competing endogenous RNA (ceRNA) targeting miR-520d-5p, with STAT3 identified as a functional target gene for miR-520d-5p in NSCLC. Furthermore, lncRNA XLOC_010706 acted as an oncogene, promoting cell proliferation and invasion while inhibiting apoptosis through the miR-520d-5p/STAT3 axis. Midazolam down-regulates the expression of lncRNA XLOC_010706, which acts as an oncogene in NSCLC. The anti-tumor effects of midazolam occur via the lncRNA XLOC_010706/miR-520d-5p/STAT3 pathway, enhancing autophagy in NSCLC. This indicates that lncRNA XLOC_010706 could serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients.
麻醉和围手术期管理对早期和中期癌症患者的长期预后有显著影响。咪达唑仑是一种常用的苯二氮䓬类麻醉剂，已显示出潜在的抗肿瘤作用。本研究旨在探讨咪达唑仑在非小细胞肺癌（NSCLC）中的抗肿瘤特性。使用CCK-8测定、集落形成测定和膜联蛋白V-异硫氰酸荧光素凋亡检测试剂盒I评估咪达唑仑对A549和H1650 NSCLC细胞系的抗肿瘤作用。此外，进行了体外Transwell测定，并建立了裸鼠皮下肿瘤模型以评估体内抗肿瘤作用。通过双荧光素酶报告基因测定、RT-qPCR和蛋白质免疫印迹证实了lncRNA XLOC_010706/miR-520d-5p/STAT3轴内的相互作用。咪达唑仑在体外和体内均通过促进自噬显著抑制A549和H1650细胞的增殖和侵袭，同时诱导其凋亡（P<0.05）。它还下调了肿瘤微环境中lncRNA XLOC_010706的表达（P<0.05）。在信号通路中，lncRNA XLOC_010706作为靶向miR-520d-5p的竞争性内源RNA（ceRNA）发挥作用，STAT3被确定为NSCLC中miR-520d-5p的功能靶基因。此外，lncRNA XLOC_010706作为癌基因，通过miR-520d-5p/STAT3轴促进细胞增殖和侵袭，同时抑制凋亡。咪达唑仑下调lncRNA XLOC_010706的表达，lncRNA XLOC_010706在NSCLC中作为癌基因发挥作用。咪达唑仑的抗肿瘤作用通过lncRNA XLOC_010706/miR-520d-5p/STAT3途径发生，增强了NSCLC中的自噬。这表明lncRNA XLOC_010706可作为NSCLC患者的新型诊断生物标志物和治疗靶点。
