Tranilast inhibits the cell growth of normal human keratinocytes in vitro.
Tranilast inhibits the cell growth of normal human keratinocytes in vitro.
复制标题
曲尼司特在体外抑制正常人角质形成细胞的细胞生长。
DOI：
10.1007/s00403-012-1291-8
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发表时间：
2012
影响因子：
3
通讯作者：
Takahiko Moriguchi
中科院分区：
文献类型：
--
作者：
Miyoko Mubo;Ying Zhao;Takahiko Moriguchi
曲那司特在临床上被用作治疗增生性疤痕或瘢痕疙瘩的药物。最近，角化细胞在这些疾病的发病机制中的作用已被注意到。因此，我们首先研究了曲尼司特对正常人角质形成细胞生长的影响。细胞生长实验表明，与对照组（曲尼拉斯特0）相比，加入曲尼拉斯特（5-400 μM）培养48 h后，细胞数量显著减少，且呈剂量依赖性。在形态学上，高浓度曲尼司特（200 ~ 400 μM）使细胞扩散减少，细胞体伸长，细胞面积明显减小。这种效果不是由于细胞毒性。去除曲尼司特后，100 μM曲尼司特对细胞生长的抑制作用和细胞形态的改变发生逆转。免疫组化染色显示曲尼司特处理的角化细胞F-actin和vinculin的表达呈剂量依赖性（100-400 μM）显著降低。此外，细胞周期检查显示，400 μM曲尼司特引起角质形成细胞G0/G1阻滞。根据这些数据，我们得出结论，曲尼司特抑制正常人角质形成细胞的生长，其机制之一可能是通过抑制f -肌动蛋白纤维和与细胞形成局灶性接触来减少细胞扩散。
Tranilast is used clinically as a drug for hypertrophic scars or keloids. Recently, the roles of keratinocytes in the pathogenesis of those conditions have been noted. Therefore, we first examined the effect of tranilast on the cell growth of normal human keratinocytes. A cell growth assay demonstrated that the cell number significantly decreased during 48 h cultures with the addition of tranilast (5–400 μM) compared with a control (tranilast 0) in a dose-dependent manner. Morphologically, cell spreading was decreased and the cell body was elongated with higher concentrations (200–400 μM) of tranilast, and the cell area decreased significantly. The effect was not due to cytotoxicity. The inhibition of cell growth and the changes in cell morphology by the treatment of 100 μM tranilast reversed after the removal of the tranilast. Immunohistochemical staining revealed that F-actin and vinculin expression with tranilast-treated keratinocytes decreased significantly in a dose-dependent manner (100–400 μM). In addition, cell cycle examination showed that 400 μM of tranilast caused G0/G1 arrest with the keratinocytes. From these data we concluded that tranilast inhibited the growth of normal human keratinocytes, and one of its mechanisms may involve decreasing cell spreading by inhibition of F-actin fiber and focal contact formation with the cells.