阿帕替尼诱导肝癌细胞凋亡的作用研究  

Effect of Apatinib on inducing the apoptosis of hepatocellular carcinoma cells

作　　者：吴飞 程洁 胡韵 陆军[1] 王章桂 Wu Fei;Cheng Jie;Hu Yun;Lu Jun;Wang Zhanggui(Medical School,Anhui University of Science and Technology,Huainan 232001,Anhui,China;Anhui No.2 Provincial People’s Hospital,Hefei 230001,Anhui,China)

机构地区：[1]安徽理工大学医学院,安徽淮南232001 [2]安徽省第二人民医院,安徽合肥230001

出　　处：《右江民族医学院学报》2021年第1期33-36,共4页Journal of Youjiang Medical University for Nationalities

基　　金：安徽省教育厅高校自然科学基金重点项目(KJ2016A379)。

摘　　要：目的探讨阿帕替尼诱导HepG2细胞凋亡的作用。方法细胞生长采用MTS法;凋亡率检测采用FCM法;激活半胱天冬酶-3(Cleaved-Caspase-3)、血管内皮生长因子受体-2(Vascular endothelial growth factor receptor-2,VEGFR-2)以及凋亡蛋白家族成员Bcl-2和Bax的表达采用WB法。结果人肝癌细胞HepG2在系列浓度阿帕替尼给药时增长受到抑制;在0μmol/L、1.25μmol/L、2.5μmol/L、5μmol/L和10μmol/L浓度时的抑制率依次为:0%、(17.25±0.34)%、(32.42±5.25)%、(52.13±7.31)%、(65.48±9.02)%;流式细胞仪检测凋亡率在高浓度组(10μmol/L)达到(44.37±3.48)%,免疫印迹分析表明高浓度时Caspase-3的活化增加;进一步研究发现,VEGFR-2和Bcl-2的在高浓度时表达最低,而Bax在高浓度时的表达最为显著。结论肝癌细胞在阿帕替尼处理后增长受到抑制,凋亡细胞增多,其作用机制可能与抑制VEGFR-2、Bcl-2的表达,上调Bax表达进而导致活化的Caspase-3增多有关。Objective To investigate the effect of Apatinib on apoptosis of HepG2 cells.Methods Cell proliferation was detected by MTS.The apoptosis rate was detected by FCM.Western blotting(WB)was used to detect the expressions of Cleaved-Caspase-3,Vascular Endothelial Growth Factor Receptor-2(VEGFR-2),and Bcl-2 and Bax of apoptotic protein family members.Results The proliferation of HepG2 was inhibited by Apatinib at serial concentrations.The inhibitory rates of Apatinib at 0μmol/L,1.25μmol/L,2.5μmol/L,5μmol/L and 10μmol/L were 0%,(17.25±0.34)%,(32.42±5.25)%,(52.13±7.31)%and(65.48±9.02)%,respectively.The apoptosis rate was(44.37±3.48)%in the high concentration group(10μmol/L)detected by flow cytometry.WB analysis showed that the activation of Caspase-3 increased when Apatinib was at high concentrations.Further studies showed that the expressions of VEGFR-2 and Bcl-2 were the lowest when Apatinib was at high concentrations,while the expression of Bax was the most significant when Apatinib was at high concentrations.Conclusion After treatment with Apatinib,the proliferation of HCC cells is inhibited and the apoptotic cells increase.The mechanism may be related to the inhibition of the expressions of VEGFR-2 and Bcl-2,up-regulation of Bax expression and the increase of activated Caspase-3.

关 键 词：阿帕替尼 癌 肝细胞 细胞凋亡 VEGFR-2 

分 类 号：R730.261[医药卫生—肿瘤]