Apatinib regulates the glycolysis of vascular endothelial cells through PI3K/AKT/PFKFB3 pathway in hepatocellular carcinoma  

作　　者：Yi Wu Bin-Bin Xie Bing-Liang Zhang Qing-Xin Zhuang Shi-Wei Liu Hong-Ming Pan 

机构地区：[1]Division of Cancer Medicine,Sir Run Run Shaw Medical Center,School of Medicine,Zhejiang University,Hangzhou 310016,Zhejiang Province,China [2]Section of Oncology,Ningxia Hui Autonomous Region General Hospital,Ningxia Medical University,Yinchuan 750000,Ningxia Hui Autonomous Region,China

出　　处：《World Journal of Gastroenterology》2025年第11期135-152,共18页世界胃肠病学杂志(英文)

基　　金：Supported by the National Natural Science Foundation of China,No.82100542 and No.81802842.

摘　　要：BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive malignancy in the Chinese population;the severe vascularization by the tumor makes it difficult to cure.The high incidence and poor survival rates of this disease indicate the search for new therapeutic alternatives.Apatinib became a drug of choice because it inhibits tyrosine kinase activity,mainly through an effect on vascular endothelial growth factor receptor-2,thereby preventing tumor angiogenesis.This mecha-nism of action makes apatinib effective in the treatment of HCC.METHODS This present study has investigated the effects of HCC cells on VECs,paying particular attention to changes in the glycolytic activity of VECs.The co-culture system established in the present study examined key cellular functions such as extracellular acidification rate and oxygen consumption rate.It also discusses participation of apatinib in the above processes.Core to the findings is the phosphatidylinositol 3-kinase(PI3K)/AKT/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway,emphasizing the function of phosphorylated AKT and its interaction with PFKFB3,an essential regulator of glycolysis.In the investigation,molecular mechanisms by which such a pathway could influence the above VECs functions of proliferation,migration,and tube formation were underlined through coimmunoprecipitation analysis.Besides,supplementary in vivo experiments on nude mice provided additional biological relevance to the obtained results.RESULTS The glycolytic metabolism in VECs co-cultured with HCC cells is highly active,and the increased glycolysis in these endothelial cells accelerates the malignant transformation of HCC cells.Apatinib has been shown to inhibit this glycolytic activity in the VECs.It also hinders the development,multiplication,and movement of these cells while encouraging their programmed cell death.Moreover,biological analysis revealed that apatinib mainly influences VECs by regulating the PI3K/AKT signaling pathway.Subsequent research ind

关 键 词：Apatinib Hepatocellular carcinoma Vascular endothelial cells GLYCOLYSIS Phosphatidylinositol 3-kinase Protein kinase B 6-phosphofructo-2-kinase/fructose-2 6-biphosphatase 3 

分 类 号：R73[医药卫生—肿瘤]