苹果多酚通过UHRF1抑制乳腺癌细胞的增殖和迁移

Apple polyphenol inhibited the proliferation and migration of breast cancer cell MDA-MB-231 mediated by UHRF1

目的探讨苹果多酚体外对乳腺癌细胞MDA-MB-231增殖、迁移的影响及可能的作用机制。方法对数生长期乳腺癌细胞用0、50、100、200、400和800μg/m L苹果多酚处理24、48和72 h,台盼蓝染色测细胞活力;CCK8试剂盒测细胞生长和增殖;划痕实验观察细胞迁移能力的变化;Western blot检测蛋白质表达水平。结果0~800μg/m L范围内,苹果多酚可浓度依赖性地抑制细胞活力和细胞增殖,下调泛素样含PHD和环指域1(ubiquitinlike with PHD and ring finger domain 1,UHRF1)和基质金属蛋白酶-2(matrix metalloproteinases-2,MMP2)的表达,以及UHRF1的调控靶分子DNA甲基转移酶3a(DNA methyltransferases 3a,DNMT3a)和3b(DNMT3b)的表达水平;而苹果多酚抑制细胞迁移的作用在400~800μg/m L浓度范围则比较显著。结论苹果多酚通过下调UHRF1和MMP2的表达,抑制乳腺癌细胞MDA-MB-231的活力、增殖和迁移。

Objective To investigate the effects of apple polyphenol on cell proliferation and migration of breast cancer cell line MDA-MB-231, and explore the potential mechanism. Methods The breast cancer cells in the logarithmic phase were treated with 0, 50, 100, 200, 400 and 800 p.g/mL of apple polyphenol for 24, 48 and 72 h,then Trypan blue staining was employed to detect cell vitality; CCK8 kit was used to determine cell growth and proliferation; cell migration ability was observed by scratch experiment, and the change of proteins expression level was assessed by Western blot. Results Apple polyphenol could content-dependently inhibit breast cancer cell＇s vitality and proliferation between 0 and 800 p.g/mL, decrease the proteins level of ubiquitinlike with PHD and ring finger domain 1 （ UHRF1 ） and matrix metalloproteinases-2 （MMP2） , and the protein levels of DNA methyltransferases 3a （DNMT3a） and DNMT3b, the molecular targets of UHRF1, also decreased. Apple polyphenol inhibition of cell＇ s migration was more significant between 400 and 800 txg/mL. Conclusion Apple polyphenol inhibited the vi cancer cells MDA-MB-231 and the downstream targets ty, cell growth and proliferation, and migration of breast decreasing the proteins expression of UHRF1 and MMP2, UHRF1, DNMT3a and DNMT3b, also decreased.