羟基红花黄色素A增强LY294002对人肝癌裸鼠移植瘤生长和血管生成的抑制  

Hydroxysafflor yellow A enhances the inhibition of LY294002 on the growth and angiogenesis of human hepatocellular carcinoma transplanted tumor in nude mice

作　　者：宋浩然[1,2] 林续涛 王东 王占青[2] 吴娜 白咸勇[1] 李京敏[1] Song Haoran;Lin Xutao;Wang Dong;Wang Zhanqing;Wu Na;Bai Xianyong;Li Jingmin(Department of Histology and Embryology,Binzhou Medical University,Yantai 264003,China;Emergency Department,Yantai Affiliated Hospital of Binzhou Medical University,Yantai 264003,China;Hepatological Surgery Department,Binzhou Medical University Hospital,Binzhou 256600,China)

机构地区：[1]山东省滨州医学院组织学与胚胎学教研室,烟台264003 [2]滨州医学院烟台附属医院急诊科,烟台264003 [3]滨州医学院附属医院肝胆外科,滨州256600

出　　处：《中国组织化学与细胞化学杂志》2022年第2期146-151,167,共7页Chinese Journal of Histochemistry and Cytochemistry

基　　金：山东省医药卫生科技发展计划(2018WS559);山东省自然科学基金(ZR2018PH039)。

摘　　要：目的研究羟基红花黄色素A(hydroxysafflor yellow A,HSYA)与磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/丝氨酸-苏氨酸蛋白激酶(PKB或Akt)信号通路的抑制剂(LY294002)联合用药对人肝癌细胞HepG2裸鼠移植瘤的增殖、凋亡及血管生成的影响。方法体外培养肝癌细胞HepG2并建立裸鼠移植瘤模型,随机分为对照组(Control组)、HSYA组、LY294002组及联合用药组(HSYA+LY294002组)。记录裸鼠的瘤重及移植瘤体积,HE染色观察移植瘤组织形态,免疫组织化学染色检测瘤组织Ki-67、Cleaved Caspase-3、VEGF、p-Akt的表达。结果与对照组比较,HSYA组肿瘤细胞异形性减少并出现点状坏死灶;LY294002组出现核固缩、核碎裂及明显坏死区;HSYA+LY294002组肿瘤组织内出现大片坏死区;HSYA+LY294002组瘤重和体积抑制率均高于HSYA组、LY294002组;HSYA组和LY294002组的Ki-67、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、p-Akt表达均下降,Cleaved Caspase-3表达均增高;但HSYA+LY294002组Ki-67、VEGF、p-Akt蛋白表达下降、Cleaved Caspase-3表达增高更显著。结论HSYA可能通过增强LY294002抑制PI3K/AKT信号通路的作用,抑制人肝癌细胞的增长和血管生成。Objective To investigate effect of hydroxysafflor yellow A(HSYA)combinates with LY294002,the inhibitor of phosphatidylinositol 3-kinase(PI3K)/serine-threonine protein kinase B(PKB or Akt)signaling pathway,on the proliferation,apoptosis and angiogenesis of HepG2 cells in transplanted nude mice.Methods HepG2 cells were cultured in vitro to establish the xenograft model in nude mice randomly divided into control group,HSYA group,LY294002 group and HSYA and LY294002 combination group(HSYA+LY294002 group).The weight and size of the transplanted tumor were recorded.The morphology of transplanted tumor was observed by HE staining.The expression of Ki-67,Cleaved Caspase-3,vascular endothelial growth factor(VEGF)and p-Akt in tumor tissues were detected by immunohistochemistry.Results Compared with the control group,the HSYA group had less tumor atypia and spotted and focal necrosis.There were karyopyknosis,nuclear debris and obvious necrosis in LY294002 group.HSYA+LY294002 group had large necrosis area in tumor tissues.The inhibitory rate of weight and size in HSYA+LY294002 group were higher than those in HSYA group and LY294002 group.The expression levels of Ki-67,VEGF and p-Akt were decreased,while Cleaved Caspase-3 expression was increased in HSYA group and LY294002 group.However,the expression levels of Ki-67,VEGF and p-Akt were decreased and Cleaved Caspase-3 expression was increased more significantly in combination group.Conclusion HSYA might inhibit the growth of human hepatoma cell and angiogenesis by enhancing the inhibitory effect of LY294002 on PI3K/AKT signaling pathway.

关 键 词：羟基红花黄色素A PI3K/AKT通路 LY294002 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]