Feiyanning Inhibits Invasion and Metastasis of Non-small Cell Lung Cancer by Regulating EMT via TGF-β1/Smad Signaling Pathway
10.13422/j.cnki.syfjx.20242421
- VernacularTitle:肺岩宁方通过TGF-β1/Smad信号通路调控EMT抑制非小细胞肺癌侵袭转移
- Author:
Xiaojie FU
1
;
Jia YANG
1
;
Kaile LIU
1
;
Wenjie WANG
1
;
Zhenye XU
1
;
Zhongqi WANG
1
;
Haibin DENG
1
Author Information
1. Longhua Hospital， Shanghai University of Traditional Chinese Medicine， Shanghai 200032， China
- Publication Type:Journal Article
- Keywords:
Feiyanning;
transforming growth factor-β1 （TGF-β1）/Smad signaling pathway;
epithelial-mesenchymal transition （EMT）;
non-small cell lung cancer （NSCLC）;
cancer metastasis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(12):110-120
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of the anti-cancer compound formula Feiyanning in inhibiting epithelial-mesenchymal transition （EMT） and invasion and metastasis of non-small cell lung cancer （NSCLC）. MethodsCell proliferation and activity were assessed using the cell counting kit-8（CCK-8） assay to evaluate the effect of Feiyanning on the proliferation of A549 and H1299 cells. Wound healing and Transwell assays were conducted to examine Feiyanning's impact on the metastasis of A549 and H1299 cells. The effects of Feiyanning on EMT and the transforming growth factor-β1 （TGF-β1）/Smad signaling pathway proteins in A549 and H1299 cells were detected by Western blot. Exogenous TGF-β1 was used to induce EMT in A549 and H1299 cells. The effects of Feiyanning on TGF-β1-induced NSCLC cell metastasis， EMT， and the TGF-β1/Smad pathway proteins were assessed by wound healing assay， Transwell assay， and Western blot. In vivo， an A549 lung metastasis model was established via tail vein injection in nude mice. A total of 28 SPF male nude mice were randomly divided into four groups： Model （NC） group， Feiyanning low-dose （FYN1） group， Feiyanning high-dose （FYN2） group， and the positive control group （TGF-β receptor kinase inhibitor SB431542 group）. The corresponding interventions were performed. After 40 days， the mice were euthanized， and lung metastases were analyzed. The expression of E-cadherin， N-cadherin， p-Smad2， and p-Smad3 in each group was detected by immunohistochemistry （IHC）. ResultsAfter Feiyanning intervention， compared to the blank group， Feiyanning inhibited the proliferation of A549 and H1299 cells in a concentration-dependent manner （P<0.01）. The metastasis ability of Feiyanning-treated cells was significantly decreased compared to the blank group （P<0.01）. The expression of EMT marker proteins N-cadherin and zinc finger transcription factors （Zeb1， Snail， Slug） was significantly reduced in the Feiyanning groups compared to the blank group （P<0.05， P<0.01）. The expression of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ， key proteins in the TGF-β1/Smad signaling pathway， was also significantly decreased （P<0.01）. In the TGF-β1-induced EMT model， compared to the TGF-β1 group， the cell metastasis ability in the Feiyanning groups was reduced （P<0.01）， and the expression levels of N-cadherin， Zeb1， Snail， and Slug were significantly lower （P<0.01）. The expression levels of p-Smad2/3， Smad2/3， TβRI， and TβRⅡ were also significantly reduced （P<0.01）. In vivo results showed that compared to the model group， the number of lung metastases in the FYN1， FYN2， and SB431542 groups was reduced （P<0.01）， and the range of cell infiltration was narrowed. Immunohistochemical results showed that compared to the model group， the expression of E-cadherin in the FYN1， FYN2， and SB431542 groups was increased （P<0.01）， the expression of N-cadherin decreased （P<0.05， P<0.01）， and the expression of p-Smad2 and p-Smad3， key proteins of the TGF-β1/Smad pathway， was reduced （P<0.01）. ConclusionFeiyanning inhibits the invasion and metastasis of NSCLC cells and EMT. The mechanism is related to the inhibition of TGF-β1/Smad signaling pathway.
