维A酸诱导人类恶性黑色素瘤细胞株A375凋亡的受体机制研究  

Mechanism of Receptor for Retinoids Inducing Apoptosis of Human Melanoma Cell Line A375

作　　者：牛新武[1] 冯捷[1] 彭振辉[1] 马惠群[1] 刘超[1] 袁景奕[1] 

机构地区：[1]西安交通大学第二医院皮肤科,西安710004

出　　处：《四川大学学报（医学版）》2006年第4期538-541,共4页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(批准号30070699)资助

摘　　要：目的研究维A酸诱导人类恶性黑素瘤细胞株A 375凋亡的受体机制。方法通过B ax/B cl-2免疫细胞化学染色、TUNEL法、A nnex in V/P I染色以及活性C aspase-3检测3种维A酸(9-c is-RA、at-RA and 13-c is-RA)、维A酸A受体(RAR)激动剂TTNPB和维A酸X受体(RXR)激动剂M a对A 375细胞凋亡的影响。结果维A酸和TTNPB均不同程度的上调B ax表达并下调B cl-2表达。A nnex in V/P I和TUNEL检测结果均显示维A酸和TTNPB可诱导A 375细胞凋亡,同对照相比均差异有统计学意义(P<0.05),而M a与对照组相比,差异无统计学意义(P>0.05)。活性C aspase-3分析显示,除了M a外,所有试剂均不同程度的上调C aspase-3的表达,以TTNPB的作用最强(P<0.05)。结论维A酸诱导A 375细胞凋亡的作用涉及到C aspase-3途径。维A酸诱导A 375细胞凋亡与RAR的激活可能有关,而与RXR的激活无关。Objective To investigate the mechanism of receptors for retinoids inducing apoptosis of human melanoma cell line A375. Methods 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. Results 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）. Conclusion 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.

关 键 词：维A酸 受体 凋亡 

分 类 号：R739.5[医药卫生—肿瘤]