Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate attenuates the malignant biological behaviors of non-small cell lung cancer via suppressing EGFR/PI3K/AKT/mTOR signaling pathway.

ABSTRACT

OBJECTIVE: The goal of the study is to examine the impact on the malignant biological behaviors of non-small cell lung cancer (NSCLC) of a novel coumarin derivative, ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate (C2F). It also aims to define its underlying mechanism. METHODS: NSCLC cell lines and xenograft nude mice model were conducted to explore the anti-NSCLC effects of C2F in vitro and in vivo. Then, network pharmacology analysis and molecular docking were applied to estimate the possible targets of C2F in NSCLC. Finally, the underlying mechanism of C2F against NSCLC cellular proliferation and tumor development was confirmed using inhibitors or activators of the PI3K/AKT signaling pathway. RESULTS: Our results showed that C2F was able to inhibit proliferation, migration, and invasion of NSCLC cell lines, induce cell cycle arrest and apoptosis in vitro, and prevent tumor growth in vivo. In addition, the estimated glomerular filtration rate and its downstream pathway (PI3K/AKT/mTOR) were found to be critical for the anti-NSCLC activity of C2F. CONCLUSIONS: C2F inhibits malignant biological behaviors of NSCLC by suppressing EGFR/PI3K/AKT/mTOR signaling pathway.