Mechanism of Huangqi Xiayuxue Decoction Against Hepatocellular Carcinoma via PI3K/Akt/FoxO Signaling Pathway
10.13422/j.cnki.syfjx.20260468
- VernacularTitle:基于PI3K/Akt/FoxO信号通路探讨黄芪下瘀血汤抗肝细胞癌的作用机制
- Author:
Xingru XING
1
;
Yuanzhou SHI
1
;
Jiawei WANG
1
;
Di WU
1
;
Yuyao ZHANG
2
;
Yalin WU
1
;
Du CHEN
1
;
Zhen ZHANG
3
;
Sha TIAN
1
Author Information
1. School of Integrated Chinese and Western Medicine，Hunan University of Chinese Medicine， Changsha 410208，China
2. Chinese Academy of Medical Sciences & Peking Union Medical College Hospital，Beijing 100730，China
3. Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine，Changsha 410208，China
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma;
network pharmacology;
Huangqi Xiaoyuxue decoction;
apoptosis;
phosphatidylinositol 3-kinase/protein kinase B/forkhead box O（PI3K/Akt/FoxO） signaling pathway;
replenishing Qi and activating blood
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(20):131-141
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the therapeutic effect and mechanism of Huangqi Xiayuxue decoction against hepatocellular carcinoma based on network pharmacology， animal experiments， and cell experiments. MethodsThe active ingredients and corresponding targets of Huangqi Xiayuxue decoction were screened via databases including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Hepatocellular carcinoma-related targets were retrieved from the GeneCards database. The common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. Huangqi Xiayuxue decoction-containing plasma was prepared. The cell counting kit-8 （CCK-8） assay was adopted to observe the effects of different volume fractions （5%， 10%， 15%， and 20%） of Huangqi Xiayuxue decoction-containing plasma on the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells， and the concentration for subsequent experiments was determined. Flow cytometry was adopted to detect the effects of Huangqi Xiayuxue decoction-containing plasma （5%， 10%， 15%， and 20%） on the apoptosis of MHCC-97H cells. A mouse model of subcutaneous xenograft hepatocellular carcinoma was established. The model mice were assigned into low-， medium-， and high-dose （4.63， 9.25， 18.5 g·kg-1） Huangqi Xiayuxue decoction and sorafenib （20 mg·kg-1） groups. Body mass and tumor volume of mice were dynamically monitored during the intervention period. After 3 weeks of intervention， hematoxylin-eosin （HE） staining was performed to observe tumor morphology. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay was employed to detect cell apoptosis. Immunohistochemistry （IHC） was adopted to examine the expression of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the tumor tissue. Real-time PCR and Western blot were employed to verify the changes in apoptosis-related factors and the phosphatidylinositol 3-kinase/protein kinase B/forkhead box O1 （PI3K/Akt/FoxO1） signaling pathway. ResultsA total of 220 common targets shared by Huangqi Xiayuxue decoction and hepatocellular carcinoma were screened out by network pharmacology， among which tumor protein p53 （TP53）， Akt1， and signal transducer and activator of transcription 3 （STAT3） were the core targets. Pathway enrichment analysis indicated that the common targets were involved in cell apoptosis and proliferation， as well as the PI3K/Akt and FoxO signaling pathways. Cell experiments showed that compared with the blank plasma group， all volume fractions of Huangqi Xiayuxue decoction-containing plasma inhibited the proliferation of HepG2， MHCC-97H， Hepa1-6， and Huh-7 cells （P<0.01）. The proportion of early apoptotic cells in MHCC-97H cells was increased after treatment with different volume fractions of Huangqi Xiayuxue decoction-containing plasma （P<0.01）. Animal experiments revealed that Huangqi Xiayuxue decoction inhibited the growth of tumor volume， promoted tumor cell apoptosis in the high-dose group， up-regulated the protein and mRNA levels of Bax and Caspase-3， down-regulated the protein and mRNA levels of Bcl-2， and reduced the phosphorylation level of the PI3K/Akt/FoxO1 signaling pathway （P<0.05， P<0.01）. ConclusionHuangqi Xiayuxue decoction exerts anti-hepatocellular carcinoma effects by inhibiting the activation of the PI3K/Akt/FoxO1 signaling pathway and promoting hepatocellular carcinoma cell apoptosis.
