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.

中文翻译：

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2,2-二氟-2-(2-oxo-2H-chromen-3-yl) 醋酸乙酯通过抑制 EGFR/PI3K/AKT/mTOR 信号通路减轻非小细胞肺癌的恶性生物学行为

目的 本研究的目的是探讨新型香豆素衍生物乙基 2,2-二氟-2-(2-oxo-2H-chromen-)对非小细胞肺癌 (NSCLC) 恶性生物学行为的影响。 3-基)乙酸酯(C2F)。它还旨在定义其基本机制。方法采用NSCLC细胞系和异种移植裸鼠模型，探讨C2F的体内外抗NSCLC作用。然后，应用网络药理学分析和分子对接来估计C2F在NSCLC中的可能靶点。最后，使用 PI3K/AKT 信号通路的抑制剂或激活剂证实了 C2F 抗 NSCLC 细胞增殖和肿瘤发展的潜在机制。结果我们的结果表明，C2F 能够抑制 NSCLC 细胞系的增殖、迁移和侵袭，在体外诱导细胞周期停滞和细胞凋亡，并在体内阻止肿瘤生长。此外，估计的肾小球滤过率及其下游通路（PI3K/AKT/mTOR）被发现对于 C2F 的抗 NSCLC 活性至关重要。结论 C2F通过抑制EGFR/PI3K/AKT/mTOR信号通路抑制NSCLC恶性生物学行为。