南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (11): 1693-.

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曲格列酮上调PPAR-γ抑制宫颈癌HeLa细胞ICAM-1和MMP-9表达

周晓霞,王智彪   

  • 出版日期:2014-11-20 发布日期:2014-11-20

Troglitazone suppresses ICAM-1 and MMP-9 expressions by up-regulating PPARγ in
HeLa cells

  • Online:2014-11-20 Published:2014-11-20

摘要: 目的探讨PPARγ激动剂曲格列酮对于宫颈癌HeLa细胞增殖及ICAM-1和MMP-9表达的影响。方法使用曲格列酮和/
或GW9662(PPARγ拮抗剂)对HeLa细胞进行干预。在不同时间点(0、24、48和72 h)使用MTT法对HeLa细胞活性进行测定。
在干预48 h后,使用RT-PCR和western blot对HeLa细胞ICAM-1、MMP-9 和PPARγ mRNA和蛋白进行测定。并使用EMSA对
HeLa细胞PPARγ DNA结合能力(核转录水平)进行分析。结果GW9662组、曲格列酮+GW9662组与空白对照组相比较各时
间点细胞活性未见显著统计学差异(P>0.05);但曲格列酮组与空白对照组相比较细胞活性呈时间依赖性降低,差异有显著统计
学意义(P均<0.05)。干预48 h 后,曲格列酮组ICAM-1 和MMP-9 mRNA和蛋白表达较空白对照组明显降低(P均<0.05);但
GW9662组和曲格列酮+GW9662组ICAM-1和MMP-9 mRNA和蛋白表达水平与空白对照组比较未见显著统计学差异(P均>
0.05)。曲格列酮干预后HeLa细胞PPARγ mRNA和蛋白表达水平和PPARγ核转位水平均显著增加,差异有显著统计学意义(P
均<0.05)。结论本实验表明曲格列酮可以通过促进PPARγ表达和PPARγ的核转录水平下调HeLa细胞ICAM-1和MMP-9的合
成,抑制HeLa细胞的增殖。

Abstract: Objective To investigate the effect of troglitazone, a proliferator-activated receptor-γ (PPARγ) agonist, on the
expressions of intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteainse-9 (MMP-9) and cell proliferation in
HeLa cells. Methods MTT assay was used to measure the cell viability at different time points (0, 24, 48 and 72 h) after
exposure to troglitazone. RT-PCR and Western blotting were employed to detect the mRNA and protein expressions of
ICAM-1, MMP-9 and PPARγ in the cells. Electrophoretic mobility shift assay (EMSA) was performed to assess the changes in
DNA binding activity of PPARγ. Results The viability of HeLa cells were time-dependently inhibited by troglitazone, which
also significantly reduced the mRNA and protein expressions of ICAM-1 and MMP-9 and increased PPARγ expression. The
effects of troglitazone in inhibiting the cell viability and reducing ICAM-1 and MMP-9 expressions were antagonized by the
application of the PPARγ antagonist GW9662. The result of EMSA also showed significantly increased DNA binding activity of
PPARγ in the cells exposed to troglitazone. Conclusions The PPARγ agonist troglitazone can inhibit the expression of ICAM-1
and MMP-9 in HeLa cells by up-regulating PPARγ.