LY294002抑制PI3K-Akt信号通路对人甲状腺癌细胞的影响
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江苏省科技厅国际合作计划资助(BZ2009053)


Effects of inhibition of PI3K signal pathway by LY294002 on anaplastic thyroid carcinoma cell line
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    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(0~100 μmol/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-

    Abstract:

    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 protein 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 thyroid 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.

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方海生,马 晔,刘 柳,沈美萍. LY294002抑制PI3K-Akt信号通路对人甲状腺癌细胞的影响[J].南京医科大学学报(自然科学版),2011,(6):789-793

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  • 收稿日期:2010-12-20
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