三种维A酸对皮肤鳞状细胞癌细胞SCL-1凋亡及Caspases的影响

Effects of three generations of tretinoids on the apoptosis of and caspase expressions in human cutaneous squamous cell carcinoma cell line SCL-1

目的探讨三种维A酸（全反式维A酸、阿维A及他扎罗汀）对人皮肤鳞状细胞癌细胞SCL-1的生长抑制和凋亡的诱导作用以及对Caspases的影响。方法以体外培养的SCL-1细胞为研究对象，采用四甲基噻唑蓝比色法观察三种维A酸对SCL-1细胞的生长抑制作用，ELISA及膜联蛋白V／PI法检测细胞凋亡的诱导情况，流式细胞仪检测细胞周期，Western印迹分析Caspases8和Caspases9表达。结果浓度为1×10^-5mol／L的3种维A酸均能抑制SCL-1细胞的生长，并具有时间依赖性。3种维A酸均能不同程度地诱导SCL-1细胞凋亡，将细胞阻滞于G1期，活化Caspases8和Caspases9。其中阿维A作用最为显著。结论维A酸能抑制皮肤鳞状细胞癌细胞生长及诱导凋亡，这一效应可能由死亡受体和线粒体途径共同介导。

Objective To investigate the effects of three generations of tretinoids on the apoptosis of and easpase expressions in human cutaneous squamous cell carcinoma cell line SCL-1. Methods SCL-1 cells were cultured in vitro in the presence of three tretinoins, namely all-trans retinoic acid （ATRA）, acitretin and tazarotene at a concentration of 1 × 10^-5 mol/L. On day 1, 3, 5, MTT assay and ELISA were used to detect the cell proliferation and apoptosis of these SCL-1 cells respectively; on day3, flow eytometry with Annexin V/PI was applied to analyze the cell cycle and early apoptosis, Western blot to measure the protein expressions of caspase-8 and caspase-9 in these cells. Results The growth of SCL-I cells could be inhibited by ATRA, acitretin or tazarotene of 1 × 10^-5 mol/L in a time-dependent manner （all P 〈 0.01 ）. All the three tretinoids could induce the cell apoptosis of SCL-1 cells （P 〈 0.01 ）, arrest them in Gl-phase, and activate caspase-8 and easpase-9 （F = 35.50, 25.79, respectively, both P 〈 0.01 ）. Of the three tretinoins, acitretin exerted the strongest effect on all the parameters tested. Conclusions Tretinoins can inhibit the growth and induce the apoptosis of cutaneous squamous carcinoma cells, which may be mediated through Fas- and mitochondria-way.