摘要
Abstract
OBJECTIVE:To investigate the effects of tangeretin on in vitro proliferation and invasion of human hepatocellular carcinoma HepG2 cells,and to investigate its mechanism. METHODS:After treated with 0 (blank control group),10,20,40, 60,80 µmol/L tangeretin for 24,48 h,the rate of cell proliferation was detected by CCK-8 assay,and IC50 was calculated. After treated with 0,20,30 μmol/L tangeretin for 48 h,Transwell invasion test was used to investigate the effects of tangeretin on cell invasion. The effects of tangeretin on mRNA and protein expression of E-cadherin,N-cadherin,Vimentin,Notch-1,CD44 and MMP-9 were determined by RT-PCR and Western blot assay. The phosphorylation of Akt and GSK-3β were investigated by Western blot assay. RESULTS:10-80 µmol/L tangeretin significantly inhibited in vitro proliferation of human hepatocellular carcinoma HepG2 cells in time and dose-dependent manner;proliferation rates of them were significantly lowered,compared to blank control group (P<0.05);IC50 were 55.7,23.4 μmol/L after treated for 24,48 h. After treated with 20,30 μmol/L tangeretin for 48 h, cell invasion was inhibited in HepG2 cells;mRNA and protein expression of N-cadherin,Vimentin,Notch-1,CD44 and MMP-9 decreased significantly,while those of E-cadherin increased significantly;the phosphorylated levels of Akt and GSK-3β increased;there was statistical significance between them and blank control group(P<0.05). CONCLUSIONS:Tangeretin can inhibit in vitro proliferation and invasion of human hepatocellular carcinoma HepG2 cell,which may be associated with inhibiting the expression of CK44 and MMP-9 and signal pathway of upstream Akt-GSK-3β through up-regulating the expression of Notch-1 and inhibiting epithelial-mesenchymal transition.关键词
桔皮素/人肝癌HepG2细胞/增殖/侵袭/上皮-间质转化Key words
Tangeretin/Human hepatocellular carcinoma HepG2 cells/Proliferation/Invasion/Epithelial-mesenchymal transi-tion分类
医药卫生