Graduate Institute of Biomedical Sciences, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan, ROC.
J Dermatol Sci. 2012 Aug;67(2):140-6. doi: 10.1016/j.jdermsci.2012.05.008. Epub 2012 Jun 2.
Topical indigo naturalis ointment is clinically proved to be an effective therapy for plaque-type psoriasis. Indirubin, as the active component of indigo naturalis, inhibits cell proliferation of epidermal keratinocytes. However, the detailed underlying mechanism is not fully understood.
To further investigate the anti-proliferating effects of indigo naturalis and indirubin on epidermal keratinocytes.
The decreased expression of CDC25B in indigo naturalis- or indirubin-treated epidermal keratinocytes, as revealed by cDNA microarray analysis, was studied. The CDC25B expression was examined under different serum concentrations and compared between primary and immortalized keratinocytes. The activation of EGFR and the effect of EGF on the cell proliferation and CDC25B expression were also investigated in epidermal keratinocytes. RT/real-time PCR and western blot method were used to analyze the CDC25B expression at the mRNA and protein levels, respectively.
Indigo naturalis and indirubin were confirmed to down-regulate CDC25B expression significantly at both the mRNA and protein levels. The growth-dependent expression of CDC25B was demonstrated by the increased expression in serum-stimulated and immortalized keratinocytes. The activation of EGF receptor, known to be highly expressed in psoriatic lesions, was inhibited by indigo naturalis or indirubin. The cell proliferation and CDC25B expression of epidermal keratinocytes were induced by EGF alone and confirmed to be inhibited by indigo naturalis or indirubin.
Except being a common therapeutic target in various cancers, CDC25B also plays an important role in the hyper-proliferation of epidermal keratinocytes which can be suppressed by anti-psoriatic drug indigo naturalis and its component, indirubin.
局部应用靛蓝天然软膏已被临床证实是斑块状银屑病的有效治疗方法。靛玉红作为靛蓝天然的活性成分，可抑制表皮角质形成细胞的增殖。然而，其详细的作用机制尚不完全清楚。
进一步研究靛蓝天然和靛玉红对表皮角质形成细胞的抗增殖作用。
通过 cDNA 微阵列分析，研究了靛蓝天然和靛玉红处理的表皮角质形成细胞中 CDC25B 表达的降低。在不同血清浓度下检测 CDC25B 的表达，并比较原代和永生化角质形成细胞之间的差异。还研究了表皮角质形成细胞中 EGFR 的激活以及 EGF 对细胞增殖和 CDC25B 表达的影响。采用 RT/实时 PCR 和 Western blot 方法分别分析 CDC25B 在 mRNA 和蛋白水平的表达。
靛蓝天然和靛玉红均能显著下调 CDC25B 的表达，无论是在 mRNA 还是蛋白水平。CDC25B 的表达依赖于细胞生长，在血清刺激和永生化角质形成细胞中表达增加。已知在银屑病皮损中高度表达的表皮生长因子受体（EGFR）被靛蓝天然或靛玉红抑制。EGF 单独诱导表皮角质形成细胞的增殖和 CDC25B 表达，并被靛蓝天然或靛玉红证实抑制。
除了作为各种癌症的共同治疗靶点外，CDC25B 还在表皮角质形成细胞的过度增殖中发挥重要作用，而抗银屑病药物靛蓝天然及其成分靛玉红可抑制其增殖。
