Mechanism of Feiyanning Formula in Suppressing Invasion and Metastasis of Lung Cancer Cells via Modulating Exosomal miR-328 and STAT3/c-Fos/NFATc1 Pathway
10.13422/j.cnki.syfjx.20251223
- VernacularTitle:肺岩宁方调控外泌体miR-328及STAT3/c-Fos/NFATc1通路抑制肺癌细胞侵袭转移的机制
- Author:
Junqing JI
1
;
Chengcheng ZHANG
1
;
Zhenye XU
1
;
Zhongqi WANG
1
Author Information
1. Longhua Hospital， Shanghai University of Traditional Chinese Medicine， Shanghai 200032， China
- Publication Type:Journal Article
- Keywords:
Feiyanning formula;
exosome;
miR-328;
lung cancer;
invasion and metastasis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(17):144-154
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the molecular mechanism by which Feiyanning formula（FYN） regulated exosomal miR-328 to suppress the invasion and metastasis of lung cancer. MethodsIn vitro models using low-metastatic 95C and high-metastatic 95D lung cancer cell lines， along with isolated exosomes， were established. Initially， 95C and 95D cells were cultured， and exosomes were isolated from their supernatants. The exosomes were identified using transmission electron microscopy （TEM）， nanoparticle tracking analysis （NTA）， and Western blot. Exosome uptake assays confirmed that both 95C and 95D cells could internalize exosomes derived from lung cancer patients' plasma. Cell counting kit-8 （CCK-8） assays were performed to assess the inhibitory effects of FYN （0， 0.1， 0.2， 0.4， 0.8， 1.6， 3.2， 6.4 g·L-1） on 95C and 95D cell proliferation. Subsequent experiments were divided into three groups of control， low-dose FYN （1 g·L-1）， and high-dose FYN （2 g·L-1） groups. Wound-healing and Transwell assays were used to evaluate the inhibitory effects of FYN on the migration and invasion of 95C and 95D cells. Western blot was employed to detect the protein expression levels of Janus kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3）， cellular oncogene Fos （c-Fos）， and nuclear factor of activated T cells 1 （NFATc1）. The mRNA expression of miR-328 was measured by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsLung cancer plasma-derived exosomes （EXO） enhanced the migration， invasion， and miR-328 expression levels in 95C and 95D cells （P<0.05， P<0.01）. FYN inhibited the proliferation， invasion， and metastasis of 95C and 95D cells in a dose-dependent manner （P<0.01）， with more pronounced effects on 95C cells. Additionally， FYN downregulated exosomal miR-328 expression and suppressed the protein levels of JAK2， STAT3， and its downstream target genes c-Fos and NFATc1 （P<0.01）. ConclusionFYN may inhibit lung cancer metastasis by downregulating exosomal miR-328 expression， potentially through the STAT3/c-Fos/NFATc1 signaling pathway. Further studies are warranted to elucidate its detailed mechanisms and facilitate clinical application， providing insights into traditional Chinese medicine-based strategies for lung cancer treatment.
