Investigations into the Mechanism of Phycocyanin in Modulating the Wip1/p53 Pathway to Induce Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells
10.13865/j.cnki.cjbmb.2025.03.1475
- VernacularTitle:藻蓝蛋白调控Wip1/p53通路诱导人肝癌细胞系HepG2凋亡的作用
- Author:
Yun-Xi JIA
1
;
Da HUO
;
Chao YAO
;
Min LI
;
Fu-Ling LIU
;
Hong YUAN
;
Hui-Ting XUE
;
Rui-Ping HU
Author Information
1. 内蒙古医科大学基础医学院,呼和浩特 010059
- Publication Type:Journal Article
- Keywords:
hepatocellular carcinoma(HCC);
phycocyanin;
apoptosis;
p53;
proteomics
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(5):741-752
- CountryChina
- Language:Chinese
-
Abstract:
Hepatocellular carcinoma(HCC)is difficult to detect in its early stages and current treatment methods are associated with significant side effects and a high risk of developing drug resistance.This study aims to investigate the effect of phycocyanin(PC)on the apoptosis of human HCC HepG2 cells and its potential mechanism.HepG2 cells were treated with PC at concentrations of 0.1,0.25,0.5,1,2.5,5,and 10 μg/mL for 12 h,and with 10 μg/mL PC and 2.5 μmol/L Wip1 inhibitor(Wip1i)alone or in combination for 12 and 24 h,respectively.Cell proliferation levels were assessed using the CCK-8 cell proliferation-toxicity assay kit.Apoptosis levels were measured by Annexin V-FITC/Propidium Iodide double staining combined with flow cytometry.TMT(Tandem Mass Tag)proteomics quantitative technol-ogy was applied to analyze differential protein expression.Western blotting was used to detect the expres-sion levels of Wip1,p53,and phosphorylated-p53(Ser15)proteins.The CCK-8 assay revealed that PC effectively inhibited HepG2 cell proliferation in a concentration-dependent manner,with a half-maximal inhibitory concentration(IC50)of 19.37 μg/mL.Flow cytometry results showed that PC significantly in-duced apoptosis,with an apoptosis rate of 30.40%.Quantitative proteomics analysis indicated that PC induced activation of the p53 pathway.The CCK-8 assay showed that Wip1i enhanced the cytotoxic effect of PC on HepG2 cells.Western blotting confirmed that PC inhibited Wip1 expression,induced p53 pro-tein phosphorylation,and promoted the expression of total p53 protein.Additionally,Wip1i further en-hanced PC-mediated activation of the p53 pathway,increasing the expression of p53 and pP53(S15).In conclusion,PC may induce apoptosis by inhibiting the activity of the p53 negative regulator Wip1,thereby promoting apoptosis through the Wip1/p53 pathway.