Modified Guizhi Fulingwan Regulates miR-34a-5p/DLL1/Notch Signaling Pathway to Promote Apoptosis and Inhibit Prostate Cancer
10.13422/j.cnki.syfjx.20260517
- VernacularTitle:桂枝茯苓丸加味方调控miR-34a-5p/DLL1/Notch信号通路促进细胞凋亡抗前列腺癌的机制
- Author:
Yuanguang DONG
1
;
Ying YANG
1
;
Penghao SUN
1
;
Yang HONG
1
;
Lu PAN
1
;
Jiapeng LI
1
;
Lijiang ZHOU
1
;
Di ZHANG
2
;
Mingdian YUAN
1
Author Information
1. Liaoning University of Traditional Chinese Medicine（TCM）， Shenyang 110847， China
2. Affiliated Hospital of Liaoning University of TCM， Shenyang 110032， China
- Publication Type:Journal Article
- Keywords:
modified Guizhi Fulingwan;
prostate cancer;
miR-34a-5p;
miR-34a-5p/δ-like protein 1 （DLL1）/Notch signaling pathway;
apoptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(18):122-133
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the molecular mechanism through which modified Guizhi Fulingwan （MGZFLW） promotes apoptosis and inhibits prostate cancer through the miR-34a-5p/δ-like protein 1 （DLL1）/Notch signaling pathway based on the traditional Chinese medicine theory of Yang transforming Qi while Yin constituting form. MethodsThe optimal intervention conditions of MGZFLW-containing serum and docetaxel （DXT） were screened by the cell counting kit-8 （CCK-8） method. Human prostate cancer cells （PC-3） were allocated into blank， MGZFLW （10%）， and DXT （30 nmol·L-1） groups. The effects of MGZFLW-containing serum on the migration and proliferation of PC-3 cells were evaluated by cell scratch and colony formation assays， and the apoptosis of PC-3 cells was detected by terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling （TUNEL） assay. The cells were transfected with miR-34a-5p mimics and miR-34a-5p inhibitor. The mRNA levels of miR-34a-5p， DLL1， Notch1 and its downstream effector factors Notch1 intracellular domain （NICD1）， Hes family basic helix-loop-helix transcription factor 1 （Hes1）， and hairy/enhancer-of-split related with YRPW motif 1 （Hey1） were determined by Real-time PCR. The protein levels of DLL1， Notch1， NICD1， Hes1， and Hey1 were determined by a WES fully automatic protein system. The effect of miR-34a-5p on the DLL1-mediated Notch pathway was evaluated based on the results. Further， after MGZFLW-containing serum intervention， the expression of DLL1 and Notch1 was detected by the immunofluorescence （IF） assay， and the mRNA and protein levels of miR-34a-5p/DLL1/Notch pathway-related molecules were quantified by Real-time PCR and the WES fully automatic protein system， respectively， to explore the regulatory effect of MGZFLW-containing serum on the miR-34a-5p/DLL1/Notch pathway. ResultsMGZFLW-containing serum inhibited the viability， migration， and proliferation and promote the apoptosis of PC-3 cells （P<0.01）. The overexpression of miR-34a-5p down-regulated the mRNA and protein levels of key molecules in the DLL1/Notch signaling pathway and promoted cell apoptosis （P<0.01）， while inhibition of miR-34a-5p had the opposite effects. MGZFLW-containing serum reversed the activation of the DLL1/Notch pathway and the inhibition of apoptosis caused by miR-34a-5p inhibition， up-regulated the expression of miR-34a-5p， and down-regulated the expression of related molecules in this pathway （P<0.01）. ConclusionMGZFLW can up-regulate the expression of miR-34a-5p to inhibit the DLL1/Notch signaling pathway and promote the apoptosis of prostate cancer cells， thereby inhibiting prostate cancer. This study provides experimental evidence for clarifying the molecular mechanism of the anti-prostate cancer effect of this formula.
