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Article 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.
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