Liu Chenghao, Huang Jiaqi, Cai Pengjie, Jiang Min, Chen Honglei
Department of Pathology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Pharmacol. 2025 Apr 3;16:1579126. doi: 10.3389/fphar.2025.1579126. eCollection 2025.
Non-small cell lung cancer (NSCLC) is one of the most prevalent and deadly malignancies worldwide. In previous studies, indacaterol, a drug used to manage chronic obstructive pulmonary disease, has shown antitumor activity. However, its role in the context of NSCLC remains underexplored. This study aimed to investigate indacaterol's mechanisms and potential therapeutic effects in lung cancer treatment.
Expression profiles and clinical information from the TCGA database were analyzed to explore the potential impact of the gene on the progression of NSCLC. The expression levels of the GLUT1 protein, encoded by the gene, and the MCT4 protein, encoded by the gene, were analyzed in both lung cancer and normal tissues. Techniques such as cellular thermal shift assay (CETSA), immunofluorescence, and Western blotting were employed to assess the interaction between indacaterol and GLUT1. Immunohistochemistry was used to study the expression of GLUT1 and MCT4 in human tissues. The effects of indacaterol on lung cancer cell lines were observed through wound healing and colony formation assays. Additionally, animal experiments combined with PD-L1 inhibitors were conducted to evaluate the antitumor effects of indacaterol and .
Analysis of TCGA data revealed that GLUT1 has a potential role in promoting NSCLC and may work in concert with MCT4. Indacaterol significantly inhibited the viability of NSCLC cells in a concentration-dependent manner. Molecular modeling and CETSA experiments further indicated that indacaterol may bind to GLUT1 and affect GLUT1 expression. Immunohistochemistry suggested that indacaterol also reduces the expression of MCT4, suggesting its potential to diminish the capacity of tumors to reprogram stromal metabolism. and experiments confirmed that the combination of indacaterol with PD-L1 inhibitors synergistically inhibited the proliferation and invasion of NSCLC cells.
Indacaterol, a potential inhibitor of GLUT1, has significant antitumor effects on NSCLC. Moreover, the combination of indacaterol with immune checkpoint inhibitors may further enhanced the inhibitory effects of indacaterol on NSCLC cells. Our study provides scientific evidence supporting the clinical application of indacaterol as a novel therapeutic strategy for NSCLC treatment.
非小细胞肺癌（NSCLC）是全球最常见且致命的恶性肿瘤之一。在先前的研究中，用于治疗慢性阻塞性肺疾病的药物茚达特罗已显示出抗肿瘤活性。然而，其在NSCLC中的作用仍未得到充分探索。本研究旨在探讨茚达特罗在肺癌治疗中的作用机制和潜在治疗效果。
分析来自TCGA数据库的表达谱和临床信息，以探索该基因对NSCLC进展的潜在影响。在肺癌组织和正常组织中分析该基因编码的GLUT1蛋白和该基因编码的MCT4蛋白的表达水平。采用细胞热位移分析（CETSA）、免疫荧光和蛋白质印迹等技术评估茚达特罗与GLUT1之间的相互作用。免疫组织化学用于研究GLUT1和MCT4在人体组织中的表达。通过伤口愈合和集落形成实验观察茚达特罗对肺癌细胞系的影响。此外，进行了结合PD-L1抑制剂的动物实验，以评估茚达特罗和的抗肿瘤作用。
对TCGA数据的分析表明，GLUT1在促进NSCLC方面具有潜在作用，并且可能与MCT4协同发挥作用。茚达特罗以浓度依赖性方式显著抑制NSCLC细胞活力。分子建模和CETSA实验进一步表明，茚达特罗可能与GLUT-1结合并影响GLUT1表达。免疫组织化学表明，茚达特罗还可降低MCT4的表达，提示其有可能降低肿瘤重编程基质代谢的能力。和实验证实，茚达特罗与PD-L1抑制剂联合使用可协同抑制NSCLC细胞的增殖和侵袭。
茚达特罗作为一种潜在的GLUT1抑制剂，对NSCLC具有显著的抗肿瘤作用。此外，茚达特罗与免疫检查点抑制剂联合使用可能会进一步增强茚达特罗对NSCLC细胞的抑制作用。我们的研究提供了科学证据，支持茚达特罗作为NSCLC治疗的一种新型治疗策略的临床应用。
