Calenduloside E inhibits hepatocellular carcinoma cell proliferation and migration by down-regulating GPX4 and SLC7A11 expression through the autophagy pathway
10.12122/j.issn.1673-4254.2024.07.12
- VernacularTitle:金盏花苷E通过自噬途径下调GPX4和SLC7A11抑制肝癌细胞的增殖和迁移
- Author:
Qianyi CHEN
1
,
2
;
Shuhan SHANG
;
Huan LU
;
Sisi LI
;
Zhimian SUN
;
Xirui FAN
;
Zhilin QI
Author Information
1. 皖南医学院基础医学院生物化学与分子生物学教研室,安徽 芜湖 241002
2. 皖南医学院活性生物大分子研究安徽省重点实验室,安徽 芜湖 241002
- Keywords:
calenduside E;
glutathione peroxidase 4;
solute carrier family 7 member 11;
autophagy;
hepatocellular carcinoma
- From:
Journal of Southern Medical University
2024;44(7):1327-1335
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma(HCC)cell proliferation and migration.Methods HCC cell lines HepG2 and Huh7 treated with calenduloside E were examined for changes in cell viability using CCK-8 assay and expressions of GPX4,SLC7A11,LC3,P62 and phosphorylation of Akt/mTOR using Western blotting.The effects LY294002 and Rapamycin(the inhibitor and activator of autophagy,respectively)on proliferation and migration of calenduloside E-treated HCC cells were evaluated using EdU and Transwell assays.The TCGA database was used to explore the expression levels of GPX4 and SLC7A11 in HCC and normal liver tissues and their correlation with the patients'survival outcomes.GPX4 and SLC7A11 expressions were also detected in HCC cells and normal hepatocytes using RT-qPCR and Western blotting.Results Calenduloside E obviously inhibited the viability of HCC cells.GPX4 and SLC7A11 were highly expressed in HCC tissues and cell lines,and their expression levels were negatively correlated with the patients'survival.In HCC cell lines,calenduloside E significantly inhibited the expressions of GPX4 and SLC7A11 proteins,activated the Akt-mTOR pathway,and enhanced the expression of LC3 II.The inhibitory effect of calenduloside E on GPX4 and SLC7A11 expressions was significantly enhanced by rapamycin but attenuated by LY294002.Inhibiting the autophagy pathway obviously diminished the inhibitory effect of calenduloside E on proliferation and migration of HCC cells,while activating this pathway produced the opposite effect.Conclusion Calenduside E inhibits the proliferation and migration of HCC cells by down-regulating GPX4 and SLC7A11 expression via the autophagy pathway.
