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

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:76

Enthalten in:

The Journal of pharmacy and pharmacology - 76(2024), 3 vom: 04. März, Seite 269-282

Sprache:

Englisch

Beteiligte Personen:

Zou, Liyi [VerfasserIn]
Li, Xiaodan [VerfasserIn]
Lin, Jiansuo [VerfasserIn]
Fang, Xuehong [VerfasserIn]
Lin, Jie [VerfasserIn]
Zhang, Lu [VerfasserIn]
Zhang, Yan [VerfasserIn]
Liang, Yanwen [VerfasserIn]
Ren, Jianwei [VerfasserIn]
Liu, Yi [VerfasserIn]
Huang, Zunnan [VerfasserIn]

Links:

Volltext

Themen:

Acetates
EC 2.7.1.-
EC 2.7.11.1
EGFR
Ethyl 2,2-difluoro-2-(2-oxo-2H-chromen-3-yl) acetate
Journal Article
Malignant biological behaviors
Non-small cell lung cancer
PI3K/AKT/mTOR
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases

Anmerkungen:

Date Completed 05.03.2024

Date Revised 05.03.2024

published: Print

Citation Status MEDLINE

doi:

10.1093/jpp/rgae008

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM367316870