ACT001 Inhibits Tumor Progression and Modulates Immune Responses in Non-Small Cell Lung Cancer

IF 2.9 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis Pub Date : 2025-08-20 DOI:10.1002/jcla.70066

Zhijing Shi, Yiman Li, Huijie Hou, Zhitao Wang, Hui Guo, Yang Yu, Yan Song, Zhe Chen

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引用次数: 0

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

ACT001 exhibits antitumoral and immunomodulatory potential by targeting STAT1/STAT3 and regulating PD-L1, offering a promising therapeutic approach for NSCLC.

Abstract Image

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ACT001抑制非小细胞肺癌的肿瘤进展和调节免疫反应。

背景：非小细胞肺癌（NSCLC）治疗的进展改善了预后，但免疫反应低、耐药和副作用等挑战仍然存在。ACT001是一种新型的小分子抑制剂，有望解决这些问题。方法：评价ACT001在非小细胞肺癌中的抗肿瘤和免疫调节作用。体外，评估其对增殖、迁移、侵袭和细胞周期阻滞的影响。在体内研究其对C57BL/6小鼠肿瘤生长的影响。下拉试验和质谱分析鉴定了ACT001与STAT1/STAT3的相互作用及其对PD-L1表达的调节。结果：ACT001在体内抑制NSCLC细胞增殖、迁移和侵袭，诱导细胞周期阻滞，抑制肿瘤生长。增强CD3+ T细胞颗粒酶B释放，促进非小细胞肺癌细胞凋亡。机制上，ACT001结合STAT1/STAT3，抑制其磷酸化并降低PD-L1的表达。结论：ACT001通过靶向STAT1/STAT3和调节PD-L1，具有抗肿瘤和免疫调节的潜力，为非小细胞肺癌的治疗提供了一种有前景的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Laboratory Analysis 医学-医学实验技术

CiteScore

5.60

自引率

7.40%

发文量

584

审稿时长

6-12 weeks

期刊介绍： Journal of Clinical Laboratory Analysis publishes original articles on newly developing modes of technology and laboratory assays, with emphasis on their application in current and future clinical laboratory testing. This includes reports from the following fields: immunochemistry and toxicology, hematology and hematopathology, immunopathology, molecular diagnostics, microbiology, genetic testing, immunohematology, and clinical chemistry.