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

Title: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

Volume: 24 Issue: 11

Author(s): Jinna Liang, Panpan Lei, Xinyue Su, Jiapan Gao, Bingxi Ren, Yuxiu Zhang, Xiaoyu Ma and Weina Ma*

Affiliation:

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

Keywords: NSCLC, dauricine, VEGFR3, FLT4, cell growth, cell migration.

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.

Cite this article as:

Liang Jinna, Lei Panpan, Su Xinyue, Gao Jiapan, Ren Bingxi, Zhang Yuxiu, Ma Xiaoyu and Ma Weina*, 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, Current Cancer Drug Targets 2024; 24 (11) . https://dx.doi.org/10.2174/0115680096282997240101192452