Mechanism of isochlorogenic acid A against hepatocellular carcinoma based on PI3K/Akt/mTOR signaling pathway combined with multi-omics
- VernacularTitle:基于PI3K/Akt/mTOR信号通路联合多组学探讨异绿原酸A抗肝癌的作用机制
- Author:
Weiwei SU
1
;
Weibing JIA
2
;
Houjian REN
1
;
Xianhui SU
3
;
Huijie GAO
4
;
Zhongchao HUO
4
;
Xin HOU
3
;
Zhen WANG
3
Author Information
1. School of Clinical Medicine，Hebei University of Engineering，Hebei Handan 056000，China
2. Dept. of General Medicine，Handan Central Hospital，Hebei Handan 056000，China
3. School of Medicine，Hebei University of Engineering，Hebei Handan 056000，China
4. Dept. of Oncology，the Affiliated Hospital of Hebei University of Engineering，Hebei Handan 056000，China
- Publication Type:Journal Article
- Keywords:
isochlorogenic acid A;
hepatocellular carcinoma;
PI3K/Akt/mTOR signaling pathway;
metabolic reprogramming
- From:
China Pharmacy
2026;37(10):1258-1263
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the mechanism of isochlorogenic acid A against hepatocellular carcinoma based on the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and multi-omics technology. METHODS The invasion rate and migration rate of human hepatocellular carcinoma HepG2 cells after 48 h of intervention with 0 （control group）， 0.25 and 0.5 mg/mL isochlorogenic acid A were examined； mRNA expression of DEP domain-containing mTOR-interacting protein （DEPTOR）， the protein expressions of mTOR， PI3K and phosphatase and tensin homologue deleted on chromosome ten （PTEN）， as well as the phosphorylation level of Akt protein were determined in the cells. Metabolomics analysis was performed using liquid chromatography-tandem mass spectrometry， and differential metabolites were screened and subjected to Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis； transcriptomics monitoring was conducted by RNA sequencing， and differentially expressed genes were screened and subjected to gene ontology （GO） and KEGG pathway enrichment analyses. RESULTS Compared with the control group， intervention with 0.25 and 0.5 mg/mL isochlorogenic acid A for 48 h significantly inhibited the invasion rate and migration rate of HepG2 cells， significantly up-regulated the mRNA expression of DEPTOR and the protein expression of PTEN， and significantly down-regulated the protein expression of PI3K and the phosphorylation level of Akt protein （except for 0.25 mg/mL isochlorogenic acid A） （ P ＜0.05）. A total of 304 differential metabolites and 212 differentially expressed genes were screened by multi-omics analysis. KEGG pathway enrichment analysis suggested that isochlorogenic acid A regulated key signaling of HepG2 cell growth mainly by inhibiting the PI3K/Akt signaling pathway， synergizing with metabolic reprogramming such as mTOR signaling pathway， ferroptosis， pentose phosphate pathway and purine/pyrimidine metabo lism. CONCLUSIONS The anti-hepatocellular carcinoma effect of isochlorogenic acid A is associated with the blockade of abnormal activation of the PI3K/Akt/mTOR signaling pathway. In addition， it may also be related to the inhibition of the pentose phosphate pathway and purine/pyrimidine metabolism， as well as the induction of ferroptosis，etc.
