摘要
目的探讨全反式维A酸(ATRA)、阿维A及他扎罗汀对人黑色素瘤细胞A375凋亡及Bax/Bcl-2蛋白表达的影响及其意义。方法采用体外培养和流式细胞仪检测细胞凋亡(AnnexinV-PI法),SABC免疫细胞化学方法检测细胞Bax/Bcl-2蛋白表达情况。结果浓度均为10-5mol/L的ATRA、阿维A及他扎罗汀能不同程度地诱导了人黑色素瘤细胞A375凋亡,其中阿维A作用最为显著,凋亡率13.42%,明显高于对照组、ATRA及他扎罗汀组(均P<0.05);其次为ATRA(5.03%,明显高于对照组及他扎罗汀组,P<0.05)和他扎罗汀组(凋亡率2.88%)。3种维A酸亦使A375细胞Bax蛋白阳性表达增强而Bcl-2蛋白阳性表达减弱(P<0.05),其中阿维A作用最强,其次为ATRA和他扎罗汀。结论维A酸促进A375细胞凋亡可能部分通过以线粒体为核心的凋亡途径。阿维A可能是防治黑色素瘤的有效药物。
Objective To investigate the effects of all-trans retinoic acid （ATRA）, acitretin and tazarotene on apoptosis and Bax/Bcl-2 protein expressions of human melanoma A375 cells. Methods The effects of retinoids on apoptosis and Bax/Bcl-2 protein expressions of A375 cells in vitro were examined. Apoptosis analysis with double staining with annexin V-FITC and PI was performed using flow cytometer. SABC immunocytochemistry was employed for detection of Bax/Bcl-2 protein expressions. Results At the concentration of 1 × 10^-5 mol/L, ATRA, acitretin and tazarotene all induced apoptosis of A375 cells with apoptosis ratio of 5.03% （P〈0.05）, 13.42% （P〈0.05） and 2.88% （P〉0.05）, respectively, and acitretin induced more significant apoptosis than the other two agents （P〈0.05）. In addition, all the three agents significantly increased the number of cells positive for Bax expression and decreased the number of cells expressing Bcl-2 （P〈0.05）, among which acitretin had the strongest effects. Conclusions ATRA, acitretin and tazarotene mediate apoptosis of A375 cells possibly through, at least partially, the mitochondrial pathway. Acitretin may be utilized as a valuable alternative for treating melanoma. Key words： retinoids; human melanoma cells, A375, apoptosis; Bax/Bcl-2 proteins
出处
《第一军医大学学报》
CAS
CSCD
北大核心
2005年第8期972-974,978,共4页
Journal of First Military Medical University
基金
陕西省自然科学基金(2002C252)~~
