三氧化二砷联合维A酸对恶性黑色素瘤细胞株A375的增殖、迁移能力影响及其可能分子机制的探讨简

目的 研究三氧化二砷（As2O3）联合维A酸对恶性黑色素瘤细胞株A375的增殖、迁移能力影响及其可能的分子机制.方法 常规培养黑色素瘤细胞株A375,分为空白对照组（不含药物的DMEM处理）、As2O3组（10μmol/LAs2O3）、全反式维A酸（at-RA）组（10 μmol/L at-RA）、As2O3＋at-RA组（10.μmol/LAs2O3联合10 μmol/L at-RA）.MTT法检测细胞活力,划痕试验检测细胞迁移能力,Western-blot法检测MMP-2、Caspase-2的蛋白水平.结果 ①As2O3＋at-RA组的细胞活力为（35.8±7.3）％,低于As2O3组的（62.4±10.3）％和at-RA组的（59.3±11.3）％,差异有统计学意义（P＜ 0.05）;②As2O3＋at-RA组的迁移能力相对值为（21.3±6.3）％,低于As2O3组的（55.4±9.5）％和at-RA组的（57.1±10.4）％,差异有统计学意义（P＜ 0.05）;③As2O3＋at-RA组的Caspase-2蛋白含量为（274.1±42.4）％,高于As2O3组（175.2±29.4）％和at-RA组（181.4±23.8）％;As2O3＋at-RA组的MMP-2蛋白含量为（36.2±8.2）％,低于As2O3组（64.2±10.4）％和at-RA组（62.7±9.4）％.结论 As2O3和at-RA联合应用能够抑制黑色素瘤细胞株A375的增殖和迁移能力,这一作用可能是通过上调Caspase-2、下调MMP-2来发挥的.

Effects of arsenic trioxide and retinoids on proliferation and migration of melanoma cell line A375 and its mechanism

Objective To study the effect of arsenic trioxide （As2O3） and retinoids on proliferation and migration of melanoma cell line A375 and its mechanism.Methods Melanoma cell line A375 were cultured and divided into vacuity contrast group （treated with DMEM）,As2O3 group （treated with 10 μmol/L As2O3）,at-RA group （treated with 10 μmol/L at-RA）,As2O3＋at-RA group （treated with 10 μmol/L As2O3 and 10 μmol/L at-RA）.Then vitality was detected by MTT,migration was detected by wound-healing assay and protein level of MMP-2,Caspase-2 were detected by Westernblot.Results ①Cell vitality value of As2O3＋at-RA group （35.8±7.3）%] was lower than As2O3 group （62.4±10.3）%] and at-RA group （59.3±11.3）%].②Migration relative value of As2O3＋at-RA group （21.3±6.3）%] was lower than As2O3 group （55.4±9.5）%] and at-RA group （57.1±10.4）%].③Caspase protein level of As2O3＋at-RA group （274.1±42.4）%] was higher than As2O3 group （175.2±29.4）%] and at-RA group （181.4±23.8）%]; MMP-2 protein level of As2O3＋at-RA group （36.2±8.2）%] was lower than As2O3 group （64.2±10.4）%] and at-RA group （62.7±9.4）%].Conclusion As2O3 combined with at-RA can reduce the migration and proliferation ability of melanoma cell line A375,and down-regulation of MMP-2,up-regulation of Caspase-2 may be its possible molecular mechanism.