达鲁胺通过以依赖 FLT4 的方式调节 PTEN/AKT/mTOR 和 Ras/MEK1/2/ERK1/2 通路抑制非小细胞肺癌的发展。
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.
机构信息
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.
出版信息
Curr Cancer Drug Targets. 2024;24(11):1157-1168. doi: 10.2174/0115680096282997240101192452.
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.
目的
非小细胞肺癌（NSCLC）仍然是一种恶性程度高、预后差的实体瘤。血管内皮生长因子受体 3（FLT4，VEGFR3）在 NSCLC 细胞中过度表达，使其成为 NSCLC 治疗的潜在靶点。在本研究中，我们旨在探讨冬凌草甲素对 NSCLC 细胞的抗癌作用及其针对 FLT4 的作用机制。
方法
我们发现冬凌草甲素通过流式细胞术分析阻断 G2/M 期周期来抑制 NCI-H1299 细胞的生长。此外，冬凌草甲素还通过划痕愈合实验和 Transwell 迁移实验抑制 NCI-H1299 细胞的迁移。更重要的是，我们的实证分析发现冬凌草甲素对 NCI-H1299 细胞的抗癌作用与 FLT4 蛋白水平呈明显正相关，而在 FLT4 敲低后，这种作用会减弱。
结果
表明冬凌草甲素通过靶向 FLT4 抑制 NCI-H1299 细胞的生长和迁移。此外，冬凌草甲素抑制了 FLT4 下游途径，如 PTEN/AKT/mTOR 和 Ras/MEK1/2/ERK1/2，从而调节细胞迁移相关分子 MMP3 和细胞周期相关分子（CDK1、pCDK1-T161 和 cyclin B1）。
结论
冬凌草甲素可能是一种有前途的用于治疗 NSCLC 的 FLT4 抑制剂。
Zotero 插件