HL-5抑制HCT116细胞增殖作用及作用机制  

Inhibitory Effect of HL-5 on Proliferation of HCT116 Cells and Its Mechanism

作　　者：邹丽娟 郑莉 万丹 甘萍 ZOU Lijuan;ZHENG Li;WAN Dan;GAN Ping(The General Hospital of Western Theater Command of Chinese PLA,Chengdu,Sichuan,China 610083;State Key Laboratory of Biotherapy,Sichuan University,Chengdu,Sichuan,China 610041)

机构地区：[1]中国人民解放军西部战区总医院,四川成都610083 [2]四川大学生物治疗国家重点实验室,四川成都610041

出　　处：《中国药业》2022年第17期38-41,共4页China Pharmaceuticals

基　　金：四川省科技计划项目[2020YJ0090]。

摘　　要：目的探讨组蛋白去乙酰化酶(HDAC)/磷脂酰肌醇-3-羟激酶(PI3K)双靶点抑制剂HL-5对肿瘤细胞增殖的抑制作用和作用机制。方法选取部分实体瘤细胞株,测定HL-5与阳性药物HDAC靶点抑制剂辛二酰苯胺异羟肟酸(SAHA)、PI3K靶点抑制剂4-羟基-2,6-二甲基苯甲腈(GDC-0941)的半数抑制率(IC_(50)),评价HL-5,SAHA,GDC-0941对肿瘤细胞增殖的抑制效果;同时,采用细胞克隆形成实验考察对肿瘤细胞的杀伤能力;通过碘化丙啶(PI)染色和流式细胞仪考察HL-5对细胞周期的影响;采用蛋白免疫印迹(Westernbloting)法检测细胞周期阻滞标志分子p-H3,P21,p-cdc2(161),cdc25c的表达水平。结果HL-5对多株肿瘤细胞的IC_(50)均小于0.5μmol/L,且均优于阳性药物SAHA和GDC-0941(P<0.05);25,50,100,200,400 nmol/LHL-5对人结肠癌细胞系HCT116细胞克隆形成有很好的抑制效果(P<0.01),且呈现一定的剂量依赖关系;HL-5处理后,p-H3和P21水平升高,p-cdc2(161)和cdc25c水平降低,HCT116细胞周期阻滞在G_(2)/M期。结论HL-5具有广谱抗肿瘤细胞增殖效果,其作用机制可能与抑制肿瘤细胞克隆形成和阻滞细胞周期有关。Objective To investigate the inhibitory effect of histone deacetylase(HDAC)/phosphatidylinositol 3-hydroxy kinase(PI3K)dual-target inhibitor HL-5 on the proliferation of tumor cells and its mechanism.Methods Some solid tumor cell lines were selected to determine the half inhibition rate(IC_(50))of HL-5 and positive drugs including HDAC target inhibitor suberoylanilide hydroxamic acid(SAHA)and PI3K target inhibitor pictilisib(GDC-0941),and evaluate the inhibitory effects of HL-5,SAHA and GDC-0941 on the proliferation of tumor cells.Meanwhile,the killing ability of HL-5 on the tumor cells was investigated by the colony formation assay.The effect of HL-5 on the cell cycle was investigated by the propidium iodide(PI)staining and the flow cytometry.The expression levels of cell cycle arrest markers including p-H3,P21,p-cdc2(161)and cdc25c were detected by the Western blotting.Results The IC_(50) of HL-5 on the many lines of tumor cells was lower than 0.5μmol/L,and lower than that of positive drugs SAHA and GDC-0941(P<0.05).The 25,50,100,200,400 nmol/L of HL-5 had a good inhibitory effect on the colony formation of human colon cancer cell line HCT116(P<0.01),and showed a certain dose-dependent relationship.After adding HL-5,the expression levels of p-H3 and P21 increased,while the expression levels of p-cdc2(161)and cdc25c decreased,and the cell cycle of HCT116 was arrested in the G_(2)/M phase.Conclusion HL-5 has a broad-spectrum anti-proliferation effect on the tumor cells,and its mechanism may be related to the inhibition of tumor cell colony formation and the arrest of cell cycle.

关 键 词：组蛋白去乙酰化酶 磷脂酰肌醇-3-羟激酶 半数抑制率 克隆形成 细胞周期 作用机制 

分 类 号：R979.1[医药卫生—药品] R965[医药卫生—药学]