Zhijing Shi, Yiman Li, Huijie Hou, Zhitao Wang, Hui Guo, Yang Yu, Yan Song, Zhe Chen
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ACT001 Inhibits Tumor Progression and Modulates Immune Responses in Non-Small Cell Lung Cancer
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.
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.
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