LY294002抑制PI3K-Akt信号通路对人甲状腺癌细胞的影响  

Effects of inhibition of PI3K signal pathway by LY294002 on anaplastic thyroid carcinoma cell line

作　　者：方海生[1] 马晔[1] 刘柳[1] 沈美萍[1] 

机构地区：[1]南京医科大学第一附属医院普外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2011年第6期789-793,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省科技厅国际合作计划资助(BZ2009053)

摘　　要：目的:探讨磷脂酰肌醇3-激酶(PI3K)抑制剂2-(4-吗啉基)-8-苯基-4氢-1-苯并吡喃-4-酮(LY294002)对人甲状腺未分化癌HTH-15细胞中PI3K-丝氨酸苏氨酸激酶(Akt)信号通路、细胞生长、细胞凋亡及细胞侵袭性的影响。方法:HTH-15细胞用不同浓度(0～100μmol/L)LY294002处理,以DMSO处理作为对照组,四甲基偶氮唑盐(MTT)试验检测细胞抑制率;流式细胞仪检测细胞周期百分比;Western blot检测磷酸化Akt(p-Akt)蛋白、基质金属蛋白酶(MMP)-2蛋白表达;Transwell小室检测细胞侵袭性。结果:LY294002能抑制HTH-15细胞的增殖,且呈一定的浓度及时间依赖性,经LY294002处理组后细胞停留在G1期的百分比明显高于DMSO对照组(P<0.05);LY294002能明显抑制p-Akt蛋白和MMP-2蛋白表达,且应用LY294002后,能降低HTH-15细胞的侵袭性。结论:甲状腺未分化癌HTH-15细胞中存在有活性的PI3K-Akt通路,表达高水平的p-Akt蛋白,LY294002可能通过抑制PI3K-Akt信号通路中p-Akt的表达抑制HTH-15细胞增殖,促进细胞凋亡,降低细胞侵袭能力。Objective：To investigate the effects of phosphoinositide 3-kinase（PI3K）inhibitor LY294002 on growth,apoptosis and cell invasion of anaplastic thyroid carcinoma cell line HTH-15.Methods：To perform the experiments,cells were divided into two groups：DMSO control group and LY294002（0～100 μmol /L）treated group.The proliferation inhibitory rate of HTH-15 cells treated by different doses of LY294002 was evaluated by MTT assay;the distribution of cell cycle was calculated by flow cytometry;the pro-tein expression level of phosphorylated-Akt（p-Akt）and matrix metalloproteinases（MMP）-2 in HTH-15 cells were detected by Western blot;Transwell chamber was applied to investigate cell invasion.Results：The growth of HTH-15 cell line was inhibited by LY294002,and this inhibition was in a time and dose-dependent manner.Treated with different concentration of LY294002,the percentage of cells in G1 phase was remarkably higher than that of DMSO control group（P 〈 0.05）;And the protein expression level of p-Akt and MMP-2 in LY294002 group was significantly down-regulated compared to that of DMSO control group（P 〈 0.05）.The cell invasion capacity was also inhibited when treated with LY294002.Conclusion：PI3K-AKT pathway does exist in anaplastic thy-roid carcinoma HTH-15 cells,and LY294002 can inhibit the growth of HTT-15 cells through PI3K-Akt pathway,induce apoptosis,and reduce cell invasion ability.PI3K-Akt pathway presents an appealing therapeutic target on Anaplastic.

关 键 词：LY294002 磷脂酰肌醇3-激酶 丝氨酸苏氨酸激酶 甲状腺未分化癌细胞 基质金属蛋白酶 

分 类 号：Q813[生物学—生物工程]