六氧化四砷对乳腺癌MCF-7细胞增殖、迁移及侵袭能力的影响

摘要

目的 观察六氧化四砷(As4O6)对人乳腺癌MCF-7细胞增殖、迁移及侵袭能力的影响,探讨其作用机制.方法 体外培养人乳腺癌MCF-7细胞,不同浓度As4O6对细胞进行干预.MTT法检测细胞增殖,流式细胞术检测细胞凋亡,划痕愈合实验检测细胞迁移能力,半定量RT-PCR检测细胞周期蛋白E1(Cyclin E1)、细胞周期蛋白A2(Cyclin A2)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、p21和基质金属蛋白酶-9(MMP-9)mRNA表达情况.结果 As4O6对MCF-7细胞增殖有明显抑制作用,且呈剂量依赖性(P<0.01);与对照组(0μmol/L)比较,As4O6浓度为9、12、15μmol/L时,MCF-7细胞凋亡率明显增加(P<0.05,P<0.01);As4O6高(3μmol/L)、低(1μmol/L)浓度均可有效抑制MCF-7细胞的迁移能力(P<0.01);随As4O6浓度增加,Cyclin E1、Caspase-3、p21 mRNA表达明显升高,Cyclin A2、MMP-9 mRNA表达明显降低(P<0.05,P<0.01).结论 As4O6对乳腺癌MCF-7细胞增殖、周期、侵袭及迁移能力有明显抑制作用,其机制可能与增强Cyclin E1、Caspase-3、p21及抑制Cyclin A2、MMP-9 mRNA表达有关.%Objective To observe the effects of tetra-atsenic oxide (As4O6) on the proliferation, migration and invasion of human breast cancer MCF-7 cells; To explore its potential mechanism. Methods The human breast cancer MCF-7 cells were regarded as the research object and cultured in vitro, with different concentrations of As4O6 using to intervene in MCF-7 cells. The cell proliferation was detected by MTT assay; the flow cytometry and wound-healing assay were used to detect the cell apoptosis and migration, respectively. The expressions of Cyclin E1, Cyclin A2, Caspase 3, p21 and MMP-9 mRNA were accessed by semi quantitative RT-PCR. Results As4O6 had a significant inhibitory effect on the proliferation of MCF-7 cells in a dose dependent manner. Compared with the control group (0 μmol/L), the apoptosis rate increased significantly when the concentration of As4O6 was 9, 12, 15 μmol/L (P<0.01). Either As4O6 at high (3 μmol/L) or low (1 μmol/L) concentration could effectively inhibit the migration of MCF-7 cells (P<0.01). With the increasing concentration of As4O6, the expressions of Cyclin E1, Caspase 3, and p21 mRNA significantly increased, while the expressions of Cyclin A2 and MMP-9 mRNA significantly decreased (P<0.05, P<0.01). Conclusion As4O6 can significantly inhibit the proliferation, cycle, invasion and migration of breast cancer MCF-7 cells, and the mechanism may be related to the increase of expressions of cyclin E1, caspase 3, p21 and inhibition of expressions of cyclin A2 and MMP-9.