中华皮肤科杂志 ›› 2009, Vol. 42 ›› Issue (12): 831-834.

• 论著 • 上一篇    下一篇

罗格列酮对人黑素瘤细胞株A375体外侵袭能力的抑制及相关机制

牛李莉1,郝进2   

  1. 1. 济宁医学院附属医院
    2. 重庆医科大学附属第二医院皮肤科
  • 收稿日期:2008-11-20 修回日期:2009-07-29 出版日期:2009-12-15 发布日期:2012-03-27
  • 通讯作者: 牛李莉 E-mail:niulili623@163.com

Rosiglitazone inhibition of A375 human malignant melanoma cell invasion

  • Received:2008-11-20 Revised:2009-07-29 Online:2009-12-15 Published:2012-03-27
  • Contact: LI Li-Li E-mail:niulili623@163.com

摘要:

目的 探讨过氧化物酶体增殖物激活受体-γ(PPAR-γ)配体罗格列酮对人黑素瘤细胞体外侵袭能力的影响及机制。方法 体外培养人黑素瘤细胞株A375;噻唑蓝法(MTT)检测罗格列酮对A375细胞的增殖抑制率;RT-PCR、Western印迹检测罗格列酮对黑素瘤侵袭相关基因基质金属蛋白酶2(MMP2)、组织金属蛋白酶抑制剂2(TIMP2)表达的影响。Matrigel侵袭实验检测罗格列酮对黑素瘤细胞体外侵袭能力的影响。结果 MTT结果显示,在24 h干预点,罗格列酮浓度为10、25 μmol/L 时,对A375细胞增殖抑制率分别为(4.86 ± 0.31)%、(5.15 ± 0.52)%,细胞毒性作用不明显。罗格列酮能在mRNA和蛋白水平下调MMP2的表达(P < 0.01),并上调TIMP2 mRNA的表达(P < 0.01)。侵袭实验显示,对照组、10 μmol/L罗格列酮组、25 μmol/L罗格列酮组穿过Transwell小室膜的A375细胞数依次为210.7 ± 14.9,154.1 ± 7.7,87.3 ± 8.1,差异有统计学意义(P < 0.01)。结论 罗格列酮能抑制人黑素瘤细胞株A375的转移,可能与其下调MMP2的表达有关。

关键词: 基质金属蛋白酶2

Abstract:

Objective To explore the effect of rosiglitazone (RGZ), a ligand of peroxisome proliferator- activated receptor γ (PPARγ), on the invasiveness of A375 cells in vitro and its mechanism of action. Methods A375 human melanoma cells were cultured in vitro and treated with different concentrations of RGZ. The proliferation of the cells, mRNA expression levels of matrix metalloproteinase (MMP) 2 and tissue inhibitor of metalloproteinase (TIMP) 2, protein expression of MMP2 in A375 cells were detected by MTT assay, semi-quantitative RT-PCR and Western-blot, respectively. The invasiveness of A375 cells was detected by Matrigel invasion assay. Results MTT assay showed that the proliferation of A375 cells was inhibited by (4.86 ± 0.31)% and (5.15 ± 0.52)% under the 24-hour treatment with RGZ of 10 and 25 μmol/L, respectively, and no evident cytotoxity was observed for RGZ. Compared with untreated A375 cells, a significant decrease was observed in the mRNA and protein expression of MMP2 in A375 cells treated with RGZ of 10 and 25 μmol/L (all P < 0.05), along with an increase in the mRNA expression of TIMP2 (both P < 0.01). The count of A375 cells transmigrating through matrigel was 154.1 ± 7.7 and 87.3 ± 8.1 under the treatment with RGZ of 10 and 25 μmol/L, significantly lower than that of those without treatment (210.7 ± 14.9, both P < 0.01). Conclusions RGZ could inhibit the transmigration of A375 cells, likely by down-regulating the mRNA and protein expression of MMP2.