Dauricine Inhibits Non-small Cell Lung Cancer Development by Regulating PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2 Pathways in a FLT4-dependent Manner

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OBJECTIVE: Non-small cell lung cancer (NSCLC) is still a solid tumor with high malignancy and poor prognosis. Vascular endothelial growth factor receptor 3 (FLT4, VEGFR3) is overexpressed in NSCLC cells, making it a potential target for NSCLC treatment. In this study, we aimed to explore the anti-cancer effects of dauricine on NSCLC cells and its mechanism targeting FLT4.

METHODS: We found that dauricine inhibited the growth of NCI-H1299 cells by blocking the cycle in the G2/M phase through flow cytometry analysis. In addition, dauricine also inhibited the migration of NCI-H1299 cells by wound healing assay and transwell migration assay. More importantly, our empirical analysis found the anti-cancer effect of dauricine on NCI-H1299 cells and the protein level of FLT4 had a distinctly positive correlation, and this effect was weakened after FLT4 knockdown.

RESULTS: It is suggested that dauricine suppressed the growth and migration of NCI-H1299 cells by targeting FLT4. Furthermore, dauricine inhibited FLT4 downstream pathways, such as PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2, thereby regulating cell migration-related molecule MMP3 and cell cycle-related molecules (CDK1, pCDK1-T161, and cyclin B1).

CONCLUSION: Dauricine may be a promising FLT4 inhibitor for the treatment of NSCLC.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Current cancer drug targets - (2024) vom: 06. Feb.

Sprache:

Englisch

Beteiligte Personen:

Liang, Jinna [VerfasserIn]
Lei, Panpan [VerfasserIn]
Su, Xinyue [VerfasserIn]
Gao, Jiapan [VerfasserIn]
Ren, Bingxi [VerfasserIn]
Zhang, Yuxiu [VerfasserIn]
Ma, Xiaoyu [VerfasserIn]
Ma, Weina [VerfasserIn]

Links:

Volltext

Themen:

Cell growth
Cell migration
Dauricine
FLT4
Journal Article
NSCLC
VEGFR3

Anmerkungen:

Date Revised 07.02.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.2174/0115680096282997240101192452

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368110974