Niu Xin-wu, Feng Jie, Peng Zhen-hui, Ma Hui-qun, Liu Chao, Juan Jing-yi
Department of Dermatology, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Jul;37(4):538-41.
To investigate the mechanism of receptors for retinoids inducing apoptosis of human melanoma cell line A375.
The effects of 3 kinds of retinoids (9-cis-RA, at-RA and 13-cis-RA), of TTNPB (RAR agonist) and of Methoprene acid (Ma, RXR agonist) on apoptosis of A375 cells were studied by detecting the expression of Bcl-2/Bax and by using. Annexin V/PI staining analysis, TUNEL detection and active Caspase-3 analysis.
Retinoids and TTNPB could up-regulate the expression of Bax and down-regulate the expression of Bcl-2. The results of TUNEL and Annexin V/PI staining analysis showed that all of retinoids and TTNPB could induce apoptosis of A375 cells, compared with control group (P < 0.05); the effect of TTNPB was significantly greater than that of others (P < 0.05), but Ma was similar to the control (P > 0.05). Active Caspase-3 analysis showed that TTNPB and all of retinoids could up-regulate the expression of Caspase-3, and the effect of TTNPB was significantly greater than that of others (P < 0.05).
Caspase-3 pathway is involved in the process for retinoids inducing apoptosis of A375 cells. The activation of RAR may have relation with retinoids inducing apoptosis of A375 cells, but may have no longer relation with RXR.
探讨维甲酸受体诱导人黑色素瘤细胞系A375凋亡的机制。
通过检测Bcl-2/Bax的表达,并采用Annexin V/PI染色分析、TUNEL检测及活性Caspase-3分析,研究3种维甲酸(9-顺式维甲酸、全反式维甲酸和13-顺式维甲酸)、TTNPB(维甲酸受体激动剂)和甲氧普烯酸(Ma,维甲酸X受体激动剂)对A375细胞凋亡的影响。
维甲酸和TTNPB可上调Bax的表达,下调Bcl-2的表达。TUNEL和Annexin V/PI染色分析结果显示,与对照组相比,所有维甲酸和TTNPB均可诱导A375细胞凋亡(P < 0.05);TTNPB的作用明显强于其他药物(P < 0.05),但Ma与对照组相似(P > 0.05)。活性Caspase-3分析显示,TTNPB和所有维甲酸均可上调Caspase-3的表达,且TTNPB的作用明显强于其他药物(P < 0.05)。
Caspase-3途径参与维甲酸诱导A375细胞凋亡的过程。维甲酸受体的激活可能与维甲酸诱导A375细胞凋亡有关,但可能与维甲酸X受体不再相关。