中国药房2025，Vol.36Issue(18)：2256-2261,6.DOI:10.6039/j.issn.1001-0408.2025.18.07
表没食子儿茶素没食子酸酯提高肝癌细胞对仑伐替尼敏感性的机制
The mechanism of epigallocatechin gallate enhancing the sensitivity of hepatocellular carcinoma cells to lenvatinib
摘要
Abstract
OBJECTIVE To investigate the potential mechanism of epigallocatechin gallate(EGCG)enhancing the sensitivity of hepatocellular carcinoma(HCC)cells to lenvatinib based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.METHODS Five human HCC cell lines(HepG2,Huh-7,SMMC-7721,SNU-368 and SNU-739)were used to evaluate the effects of lenvatinib alone and in combination with EGCG on survival rates,clone number,proliferation rate,invasion number and the expressions of mRNAs and proteins related to the PI3K/Akt signaling pathway.The PI3K activator insulin-like growth factor-1(IGF-1)was introduced to investigate the effect of activating the PI3K/Akt signaling pathway on the sensitization effect of EGCG.RESULTS Compared with the control group,lenvatinib(10 μmol/L)and different concentrations of EGCG+lenvatinib(1,5 and 10 μg/mL EGCG+10 μmol/L lenvatinib)significantly reduced the survival rates and clone numbers of all five HCC cell lines in a dose-dependent manner(P＜0.05).Lenvatinib(10 μmol/L)and EGCG+lenvatinib(10 μg/mL EGCG+10 μmol/L lenvatinib)also markedly inhibited the proliferation rate and invasion numbers of these cells,and decreased the mRNA expressions of PI3K,Akt,mammalian target of rapamycin(mTOR),P70S6K and 4EBP,and the phosphorylation levels of PI3K and Akt,as well as the protein expressions of mTOR and B cell lymphoma-2(Bcl-2)in HepG2 cells or all five HCC cells;conversely,the mRNA and protein expressions of phosphatase and tensin homologue deleted on chromosome 10(PTEN),and the protein expressions of caspase-3 and cleaved caspase-3 were significantly upregulated,with more pronounced effects observed in the EGCG+lenvatinib group than in the lenvatinib group(P＜0.05).Compared with the lenvatinib group and the EGCG+lenvatinib group,the clone number,proliferation rate and invasion number of HepG2 cells in the EGCG+lenvatinib+IGF-1 group(10 μg/mL EGCG+10 μmol/L lenvatinib+50 ng/mL IGF-1)were significantly increased(P＜0.05).CONCLUSIONS EGCG can enhance the sensitivity of HCC cells to lenvatinib,and its underlying mechanism may be related to the inhibition of the activation of PI3K/Akt signaling pathway activation.关键词
表没食子儿茶素没食子酸酯/肝癌/仑伐替尼/增敏作用/PI3K/Akt信号通路Key words
epigallocatechin gallate/hepatocellular car-cinoma/lenvatinib/sensitization effect/PI3K/Akt signaling pathway分类
医药卫生引用本文复制引用
宋传芳,艾江,温超,张杰,崔江河..表没食子儿茶素没食子酸酯提高肝癌细胞对仑伐替尼敏感性的机制[J].中国药房,2025,36(18):2256-2261,6.基金项目
黑龙江省自然科学基金项目(No.2023JJ0008) （No.2023JJ0008）
