论文部分内容阅读
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 phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-4hydro-1-benzopyran-4-one (LY294002) against human thyroid gland The effects of PI3K-serine threonine kinase (Akt) signaling pathway, cell growth, apoptosis, and cell invasiveness in differentiated cancer HTH-15 cells. METHODS: HTH-15 cells were treated with different concentrations (0-100 μmol/L) of LY294002, treated with DMSO as a control group, MTT assay was used to determine the cell inhibition rate, and the percentage of cell cycle was measured by flow cytometry. Western blot was used to detect the expression of phosphorylated Akt (p-Akt) protein and matrix metalloproteinase (MMP)-2 protein; Transwell chamber was used to detect cell invasiveness. RESULTS: LY294002 inhibited the proliferation of HTH-15 cells in a certain concentration and time-dependent manner. The percentage of cells in the G1 phase after LY294002 treatment was significantly higher than that in the DMSO control group (P<0.05); LY294002 significantly inhibited the proliferation of HTH-15 cells. The expression of p-Akt protein and MMP-2 protein, and the application of LY294002, can reduce the invasiveness of HTH-15 cells. CONCLUSION: There is an active PI3K-Akt pathway in the anaplastic thyroid cancer HTH-15 cells, which expresses high levels of p-Akt protein. LY294002 may inhibit the proliferation of HTH-15 cells by inhibiting the expression of p-Akt in the PI3K-Akt signaling pathway. Promote cell apoptosis and reduce cell invasion.