Zhang M-L, Tao Y, Zhou W-Q, Ma P-C, Cao Y-P, He C-D, Wei J, Li L-J
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, China.
Clin Exp Dermatol. 2014 Apr;39(3):354-60. doi: 10.1111/ced.12227.
All-trans retinoic acid (ATRA) has been tried for the treatment and prevention of a number of epithelial cancers. However, the precise mechanism by which ATRA inhibits the growth of cutaneous squamous cell carcinoma (cSCC) remains elusive.
To determine the suppressive effects of ATRA on the human cSCC cell line SCL-1, and explore the possible mechanisms involved.
SCL-1 cells were treated with ATRA, then cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while apoptosis and cell cycle progression were analysed by flow cytometry. Protein levels of cell-cycle regulatory proteins and the activation of extracellular signal-regulated kinase (ERK) and Jun kinase (JNK) were detected by western blotting analysis. Transcriptional activity of activator protein (AP)-1 was examined by luciferase reporter assay.
ATRA inhibited the proliferation of SCL-1 cells and had modest proapoptotic effects. ATRA also induced G1 cell-cycle arrest, inhibited the expression of cyclin D1/cyclin-dependent kinase (CDK)4 and cyclinE/CDK2, and increased the expression of the cyclin-dependent kinase inhibitors p21 and p27. In addition, ATRA significantly decreased the phosphorylation of ERK1/2 and JNK1/2, and inhibited AP-1 transcriptional activity.
ATRA induces cell-cycle arrest in human cSCC cells by inhibiting the mitogen-activated protein kinase (MAPK)-AP1 pathway, and could be effective in the prevention and chemotherapy of human cSCC.
全反式维甲酸（ATRA）已被尝试用于多种上皮癌的治疗和预防。然而，ATRA抑制皮肤鳞状细胞癌（cSCC）生长的确切机制仍不清楚。
确定ATRA对人cSCC细胞系SCL-1的抑制作用，并探讨其可能的作用机制。
用ATRA处理SCL-1细胞，然后通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法检测细胞增殖，同时通过流式细胞术分析细胞凋亡和细胞周期进程。通过蛋白质印迹分析检测细胞周期调节蛋白的蛋白质水平以及细胞外信号调节激酶（ERK）和Jun激酶（JNK）的激活情况。通过荧光素酶报告基因检测法检测激活蛋白（AP）-1的转录活性。
ATRA抑制SCL-1细胞的增殖，并具有适度的促凋亡作用。ATRA还诱导G1期细胞周期停滞，抑制细胞周期蛋白D1/细胞周期蛋白依赖性激酶（CDK）4和细胞周期蛋白E/CDK2的表达，并增加细胞周期蛋白依赖性激酶抑制剂p21和p27的表达。此外，ATRA显著降低ERK1/2和JNK1/2 的磷酸化水平，并抑制AP-1的转录活性。
ATRA通过抑制丝裂原活化蛋白激酶（MAPK）-AP1途径诱导人cSCC细胞的细胞周期停滞，可能对人cSCC的预防和化疗有效。
