Brusatol Suppresses Proliferation of Human Gastric Cancer HGC-27 Cells Through Inducing Ferroptosis via Nrf2/HO-1 Pathway
10.13422/j.cnki.syfjx.20221628
- VernacularTitle:鸦胆子苦醇通过Nrf2/HO-1通路诱导细胞铁死亡抑制胃癌细胞HGC-27增殖
- Author:
Wei GAO
1
;
Hairong ZENG
1
;
Jiamin LE
1
Author Information
1. Changhai Hospital， Naval Medical University， Shanghai 200433， China
- Publication Type:Journal Article
- Keywords:
brusatol;
gastric cancer;
ferroptosis;
reactive oxygen species;
lipid peroxidation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(2):81-87
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study effect of brusatol （BR） on proliferation of human gastric cancer HGC-27 cells and its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the survival rate of HGC-27 cells at different concentrations of BR. HGC-27 cells were treated with BR （7.5， 15， 30 μmol·L-1） for 24 h， and then the cell clone formation was analyzed. 2，7-Dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescent probe and lipid peroxidation sensor （C11-BODIPY） were employed to detect the levels of intracellular reactive oxygen species （ROS） and lipid peroxidation， respectively. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the messenger ribonucleic acid （mRNA） and protein expressions of solute carrier family 7 member 11 （SLC7A11）， glutathione peroxidase 4 （GPX4）， solute carrier family 40 member 1 （SLC40A1）， transferrin， nuclear factor E2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1）， respectively. ResultThe survival rate of HGC-27 cells was decreased with the increase of BR concentration， and the IC50 was 15.34 μmol·L-1. Compared with the conditions in blank group， the cell clone formation of BR （7.5， 15， 30 μmol·L-1） groups was inhibited in a dose-dependent manner （P<0.05，P<0.01）， while the levels of intracellular ROS and lipid peroxidation， iron concentration， and lactic dehydrogenase （LDH） leakage were increased in a dose-dependent manner （P<0.05，P<0.01）. Compared with the blank group， the BR （15， 30 μmol·L-1） groups lowered the mRNA and protein expressions of SLC7A11， GPX4， SLC40A1， Nrf2 and HO-1， while elevated the mRNA and protein expression of TRF in a dose-dependent manner （P<0.05，P<0.01）. ConclusionBR suppressed the proliferation of HGC-27 cells through inducing ferroptosis via inhibiting Nrf2/HO-1 pathway.
