Shi Zhijing, Li Yiman, Hou Huijie, Wang Zhitao, Guo Hui, Yu Yang, Song Yan, Chen Zhe
Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.
Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, China.
J Clin Lab Anal. 2025 Sep;39(17):e70066. doi: 10.1002/jcla.70066. Epub 2025 Aug 20.
Advancements in non-small cell lung cancer (NSCLC) therapies have improved outcomes, but challenges like low immune response, drug resistance, and side effects persist. ACT001, a novel small-molecule inhibitor, shows promise in addressing these issues.
We evaluated ACT001's anti-tumor and immunomodulatory effects in NSCLC. In vitro, its impact on proliferation, migration, invasion, and cell cycle arrest was assessed. In vivo, its effect on tumor growth in C57BL/6 mice was studied. Pull-down assays and mass spectrometry identified ACT001's interaction with STAT1/STAT3 and its regulation of PD-L1 expression.
ACT001 inhibited NSCLC cell proliferation, migration, and invasion, induced cell cycle arrest, and suppressed tumor growth in vivo. It enhanced granzyme B release in CD3 T cells, promoting NSCLC cell apoptosis. Mechanistically, ACT001 bound to STAT1/STAT3, suppressing their phosphorylation and reducing PD-L1 expression.
ACT001 exhibits antitumoral and immunomodulatory potential by targeting STAT1/STAT3 and regulating PD-L1, offering a promising therapeutic approach for NSCLC.
非小细胞肺癌（NSCLC）治疗的进展改善了治疗效果，但诸如免疫反应低下、耐药性和副作用等挑战仍然存在。新型小分子抑制剂ACT001在解决这些问题方面显示出前景。
我们评估了ACT001在NSCLC中的抗肿瘤和免疫调节作用。在体外，评估了其对增殖、迁移、侵袭和细胞周期阻滞的影响。在体内，研究了其对C57BL/6小鼠肿瘤生长的影响。下拉实验和质谱分析确定了ACT001与STAT1/STAT3的相互作用及其对PD-L1表达的调节。
ACT001抑制NSCLC细胞增殖、迁移和侵袭，诱导细胞周期阻滞，并在体内抑制肿瘤生长。它增强了CD3 T细胞中颗粒酶B的释放，促进NSCLC细胞凋亡。从机制上讲，ACT001与STAT1/STAT3结合，抑制其磷酸化并降低PD-L1表达。
ACT001通过靶向STAT1/STAT3和调节PD-L1展现出抗肿瘤和免疫调节潜力，为NSCLC提供了一种有前景的治疗方法。
