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Dauricine Inhibits Non-small Cell Lung Cancer Development by Regulating PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2 Pathways
Jinna Liang1,2, Panpan Lei1,2, Xinyue Su1,2
1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, P.R. China.
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.
Insights
Dauricine effectively inhibits non-small cell lung cancer (NSCLC) growth and migration by targeting vascular endothelial growth factor receptor 3 (FLT4). This study highlights dauricine as a potential therapeutic agent for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) presents significant challenges due to its high malignancy and poor prognosis.
- Vascular endothelial growth factor receptor 3 (FLT4, also known as VEGFR3) is overexpressed in NSCLC cells, identifying it as a potential therapeutic target.
Purpose of the Study:
- To investigate the anti-cancer effects of dauricine on NSCLC cells.
- To elucidate the mechanism by which dauricine exerts its effects, specifically its targeting of FLT4.
Main Methods:
- Flow cytometry was used to analyze cell cycle progression.
- Wound healing and transwell migration assays assessed cell migration.
- FLT4 protein levels were correlated with dauricine's anti-cancer effects, and FLT4 knockdown was performed to validate its role.
Main Results:
- Dauricine inhibited NCI-H1299 cell growth by arresting the cell cycle at the G2/M phase.
- Dauricine significantly reduced NCI-H1299 cell migration.
- A positive correlation was observed between dauricine's anti-cancer activity and FLT4 protein levels, which was diminished upon FLT4 knockdown.
Conclusions:
- Dauricine demonstrates anti-cancer effects on NSCLC cells by targeting FLT4.
- Dauricine modulates downstream signaling pathways including PTEN/AKT/mTOR and Ras/MEK1/2/ERK1/2.
- Dauricine regulates key molecules involved in cell migration (MMP3) and cell cycle progression (CDK1, pCDK1-T161, cyclin B1).
- Dauricine shows promise as a potential FLT4 inhibitor for NSCLC treatment.
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