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
x
请在关注微信后,向客服人员索取文件
篇名: | 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 |
TITLE: | The mechanism of epigallocatechin gallate enhancing the sensitivity of hepatocellular carcinoma cells to lenva-tinib |
摘要: | 目的 基于磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路探讨表没食子儿茶素没食子酸酯(EGCG)提高肝癌细胞对仑伐替尼敏感性的潜在机制。方法以HepG2、Huh-7、SMMC-7721、SNU-368、SNU-7395种人肝癌细胞为对象,探讨仑伐替尼、EGCG+仑伐替尼对细胞存活率、克隆形成数、增殖率、侵袭数和通路相关mRNA及蛋白表达的影响;引入PI3K激动剂[胰岛素样生长因子1(IGF-1)],考察激活PI3K/Akt信号通路对EGCG增敏作用的影响。结果与对照组比较,仑伐替尼组(10μmol/L)、不同质量浓度EGCG+仑伐替尼组(1、5、10μg/mLEGCG+10μmol/L仑伐替尼)5种肝癌细胞的存活率和克隆形成数均呈浓度依赖性降低(P<0.05);仑伐替尼组(10μmol/L)、EGCG+仑伐替尼组(10μg/mLEGCG+10μmol/L仑伐替尼)5种肝癌细胞的增殖率和侵袭数,HepG2细胞或5种细胞中PI3K、Akt、哺乳动物雷帕霉素靶蛋白(mTOR)、P70S6K、4EBPmRNA的表达以及PI3K、Akt蛋白的磷酸化水平和mTOR、B细胞淋巴瘤2(Bcl-2)蛋白的表达均显著降低或下调,而第10号染色体缺失的磷酸酶及张力蛋白同源物(PTEN)mRNA及蛋白、胱天蛋白酶3(caspase-3)、剪切的胱天蛋白酶3(cleavedcaspase-3)的表达均显著上调(P<0.05);且EGCG+仑伐替尼组上述指标的变化较仑伐替尼组更为显著(P<0.05)。与仑伐替尼组、EGCG+仑伐替尼组比较,EGCG+仑伐替尼+IGF-1组(10μg/mLEGCG+10μmol/L仑伐替尼+50ng/mLIGF-1)HepG2细胞的克隆形成数、增殖率及侵袭数均显著升高(P<0.05)。结论EGCG可增加肝癌细胞对仑伐替尼的敏感性,其作用机制可能与抑制PI3K/Akt信号通路激活有关。 |
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. |
期刊: | 2025年第36卷第18期 |
作者: | 宋传芳;艾江;温超;张杰;崔江河 |
AUTHORS: | SONG Chuanfang,AI Jiang,WEN Chao,ZHANG Jie,CUI Jianghe |
关键字: | 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 |
KEYWORDS: | epigallocatechin gallate; hepatocellular car- |
阅读数: | 5 次 |
本月下载数: | 0 次 |
* 注:未经本站明确许可,任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作!