磷脂酰肌醇3激酶抑制药(LY294002)对结肠癌细胞的作用  

Effects of phosphatidylinositol 3 kinase inhibitor (LY294002) on the colon cancer cells

作　　者：张小鸿 袁平[1,2] ZHANG Xiao-hong;YUAN Ping(Depatment of Laboratory Quality Management,Fujian Center for Disease Prevention and Control,Fuzhou 35001,Fujian Province,China;Key Laboratory of zoology in Fujian Province,Fuzhou 35001,Fujian Province,China)

机构地区：[1]福建省疾病预防控制中心质管科,福建福州350001 [2]福建省人兽共患病实验室,福建福州350001

出　　处：《中国临床药理学杂志》2021年第19期2636-2639,共4页The Chinese Journal of Clinical Pharmacology

基　　金：福建省卫生健康科技计划基金资助项目(2018-1-23,2015-ZQN-JC-9)。

摘　　要：目的探讨磷脂酰肌醇3激酶(PI3K)抑制药—2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4酮(LY294002)对HCT116结肠癌细胞增殖、凋亡、黏附和侵袭的影响和其机制。方法以6个浓度(1.25,2.50,5.00,0.00,20.00,40.00μmol·L^(-1))的LY294002处理HCT116细胞,以四甲基偶氮唑盐实验测定半抑制率(IC50)。将细胞随机分为2组:对照组和LY294002组。以烟酸己可碱/碘化丙啶实验检测细胞凋亡;黏附实验检测细胞黏附能力;Transwell检测细胞侵袭情况;蛋白质印迹法检测PI3K蛋白相对表达水平和蛋白激酶B(Akt)、肿瘤坏死因子-κB(NF-κB)的磷酸化水平。结果 LY294002处理HCT116细胞IC50为13.55μmol·L^(-1)。对照组、LY294002组的细胞凋亡率分别为(3.56±0.37)%和(36.47±3.89)%;细胞黏附率分别为(98.59±9.27)%和(58.36±5.86)%;细胞侵袭数目分别为(173.82±12.48)和(59.60±5.96)个;PI3K蛋白相对表达水平分别为0.98±0.10和0.19±0.01;p-Akt相对表达水平分别为0.99±0.10和0.08±0.01;p-NF-κB p65相对表达水平分别为0.82±0.08和0.16±0.01。组间比较,上述指标的差异均有统计学意义(均P <0.05)。结论 LY294002能显著地抑制HCT116细胞增殖、黏附和侵袭,并诱导细胞凋亡,与阻断PI3K/Akt/NF-κB信号通路有关。Objective To explore effects and mechanism of phosphatidylinositol 3 kinase(PI3K) inhibitor 2-(4-morpholine)-8-phenyl-4 hydrogen-1-benzo-4 ketone(LY294002) on proliferation,apoptosis,adhesion and invasion of colon cancer cell.Methods HCT116 cells were treated with 6 concentrations(1.25,2.50,5.00,0.00,20.00,40.00 μmol·L^(-1) LY294002),and half maximalinhibitory rate(IC50) was determined by tetramethylazozolium salt.The cells were randomly divided into two groups:control group and LY294002 group.Cell apoptosis was detected by Hoechst/propidium iodide assay.Cell adhesion was detected by adhesion assay.Cell invasion was detected by Transwell assay.The relative expression of PI3K protein,phosphorylation of protein kinase B(Akt) and tumor necrosis factor-κB p65(NF-κB p65) were detected by Western blot.Results The IC50 of HCT116 cells treated with LY294002 was 13.55 μmol·L^(-1).Cell apoptotic rate in control group and LY294002 group were(3.56±0.37) %,(36.47±3.89) %,respectively;cell adhesion rate was(98.59±9.27) %,(58.36±5.86) %,respectively;the number of cell invasion was(173.82±12.48),(59.60±5.96) cell,respectively;the relative expression of PI3K was 0.98±0.10,0.19±0.01,respectively;the relative expression of p-Akt was 0.99±0.10,0.08±0.01,respectively;the relative expression of p-NF-κB p65 was 0.82±0.08,0.16±0.01,respectively.There were significant differences in the above indexes between the two groups(all P <0.05).Conclusion LY294002 could significantly inhibit the proliferation,adhesion and invasion of HCT116 cells,and induce apoptosis,which was related to blocking PI3K/Akt/NF-κB signaling pathway.

关 键 词：2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4酮 HCT116结肠癌细胞 磷脂酰肌醇3激酶/蛋白激酶B/肿瘤坏死因子-κB信号通路 增殖 凋亡 黏附 侵袭 

分 类 号：R97[医药卫生—药品]