Ran Li-wei, Tan Sheng-shun, Wang Wan-juan, Qiu Shi, Lei Xiao-bing, Zeng Wei-hui
Department of Dermatology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Di Yi Jun Yi Da Xue Xue Bao. 2005 Aug;25(8):972-4, 978.
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.
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.
At the concentration of 1 x 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.
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.
探讨全反式维甲酸(ATRA)、阿维A和他扎罗汀对人黑素瘤A375细胞凋亡及Bax/Bcl-2蛋白表达的影响。
检测维甲酸类药物对体外培养的A375细胞凋亡及Bax/Bcl-2蛋白表达的影响。采用流式细胞仪通过Annexin V-FITC和PI双染法进行凋亡分析。运用SABC免疫细胞化学法检测Bax/Bcl-2蛋白表达。
在浓度为1×10⁻⁵ mol/L时,ATRA、阿维A和他扎罗汀均诱导A375细胞凋亡,凋亡率分别为5.03%(P<0.05)、13.42%(P<0.05)和2.88%(P>0.05),阿维A诱导的凋亡比其他两种药物更显著(P<0.05)。此外,这三种药物均显著增加Bax表达阳性细胞数并减少Bcl-2表达细胞数(P<0.05),其中阿维A的作用最强。
ATRA、阿维A和他扎罗汀可能至少部分通过线粒体途径介导A375细胞凋亡。阿维A可作为治疗黑素瘤的一种有价值的替代药物。