HDAC1调控Wnt/β-catenin信号通路对乳腺癌细胞凋亡的影响  

Effect of Wnt/β-catenin signaling pathway regulated by HDAC1 on apoptosis of breast cancer cells

作　　者：牟成金 潘武 李娟 汪静[2] MOU Cheng-jin;PAN Wu;LI Juan;WANG Jing(Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital (East Hospital),Chengdu 610101,China;Department of Breast Surgery,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川省医学科学院四川省人民医院(东院),四川成都610101 [2]四川大学华西医院乳腺外科,四川成都610041

出　　处：《中国病理生理杂志》2019年第1期41-47,共7页Chinese Journal of Pathophysiology

基　　金：四川省科技厅科研项目(No.2015SZ0070)

摘　　要：目的:研究组蛋白脱乙酰酶1(HDAC1)对乳腺癌细胞凋亡的影响及机制。方法:RT-qPCR和Western blot法分别测定正常乳腺上皮细胞系MCF-10A和乳腺癌细胞系BT549、MCF-7和MDA-MB-231中HDAC1的m RNA和蛋白水平。在MDA-MB-231细胞中转染HDAC1 si RNA,RT-qPCR和Western blot测定HDAC1的表达水平,MTT法测定细胞活力,流式细胞术测定凋亡,Western blot测定细胞中β-连环蛋白(β-catenin)、c-Myc、细胞周期蛋白D1(cyclin D1)和cleaved caspase-3的蛋白水平。用Wnt/β-catenin信号通路激活剂处理下调HDAC1表达后的乳腺癌细胞,测定细胞活力和凋亡。结果:乳腺癌细胞系BT549、MCF-7和MDA-MB-231中HDAC1的m RNA和蛋白水平均明显高于正常乳腺上皮细胞系MCF-10A(P <0. 01),并且MDA-MB-231细胞中的HDAC1水平最高。HDAC1 si RNA可以降低乳腺癌细胞中HDAC1的m RNA和蛋白水平。敲减HDAC1表达后的MDA-MB-231细胞活力降低,细胞凋亡率升高,细胞中cleaved caspase-3水平升高,β-catenin、c-Myc和cyclin D1的蛋白水平降低(P <0. 05)。Wnt/β-catenin信号通路激活剂可以逆转HDAC1下调诱导的MDA-MB-231细胞凋亡和细胞活力降低,减少cleaved caspase-3的水平(P <0. 05)。结论:敲减HDAC1的表达可以通过抑制Wnt/β-catenin信号通路的激活诱导乳腺癌细胞凋亡。AIM:To study the effect of histone deacetylase 1(HDAC1)on the apoptosis of breast cancer cells.METHODS:The expression of HDAC1 at mRNA and protein levels in normal mammary epithelial cell line MCF-10A and breast cancer cell lines BT549,MCF-7 and MDA-MB-231 was measured by RT-qPCR and Western blot.HDAC1 siRNA was transfected into MDA-MB-231 cells,and then RT-qPCR and Western blot were used to determine the expression level of HDAC1.The cell viability was measured by MTT assay,and apoptosis was analyzed by flow cytometry.The protein levels ofβ-catenin,c-Myc,cyclin D1 and cleaved caspase-3 were determined by Western blot.Breast cancer cells with HDAC1 knockdown were treated with Wnt/β-catenin signaling pathway activator,and then the cell viability and apoptosis were measured.RESULTS:The expression of HDAC1 at mRNA and protein levels in BT549,MCF-7 and MDA-MB-231 cells was significantly higher than that in normal mammary epithelial cell line MCF-10A,and the highest expression level of HDAC1 was observed in MDA-MB-231 cells(P<0.05).HDAC1 siRNA reduced the expression of HDAC1 at mRNA and protein levels in the breast cancer cells.The viability of MDA-MB-231 cells was decreased after knockdown of HDAC1 expression,the apoptotic rate was increased,the protein level of cleaved caspase-3 in the cells was elevated,and the protein levels ofβ-catenin,c-Myc and cyclin D1 were decreased(P<0.05).Wnt/β-catenin signaling pathway activator reversed HDAC1 knockdown-induced apoptosis and decrease in viability of MDA-MB-231 cells,and reduced the protein level of cleaved caspase-3.CONCLUSION:Knockdown of HDAC1 expression induces apoptosis of breast cancer cells by inhibiting the activation of Wnt/β-catenin signaling pathway.

关 键 词：细胞凋亡 乳腺癌 组蛋白脱乙酰酶1 WNT/Β-CATENIN信号通路 

分 类 号：R737.9[医药卫生—肿瘤] R730.23[医药卫生—临床医学]