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

Jinna Liang; Panpan Lei; Xinyue Su; Jiapan Gao; Bingxi Ren; Yuxiu Zhang; Xiaoyu Ma; Weina Ma

doi:10.2174/0115680096282997240101192452

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

Curr Cancer Drug Targets. 2024 Feb 6. doi: 10.2174/0115680096282997240101192452. Online ahead of print.

Authors

Jinna Liang^{1

2}, Panpan Lei^{1

2}, Xinyue Su^{1

2}, Jiapan Gao^{1

2}, Bingxi Ren^{1

2}, Yuxiu Zhang^{1

2}, Xiaoyu Ma^{1

2}, Weina Ma^{1

2}

Affiliations

¹ School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, P.R. China.
² State Key Laboratory of Shaanxi for Natural Medicines Research and Engineering, Xi'an 710061, P.R. China.

PMID: 38321898
DOI: 10.2174/0115680096282997240101192452

Abstract

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.

Keywords: Cell growth; Cell migration; Dauricine; FLT4; NSCLC; VEGFR3.