HDAC抑制剂下调乳腺癌细胞系HER-2的表达及miRNA表达谱的变化

发布时间：2018-06-25 18:18

本文选题：HDAC抑制剂 + 乳腺癌　；参考：《中国肿瘤临床》2017年13期

【摘要】：目的:探讨组蛋白去乙酰化酶(histone deacetylase,HDAC)抑制剂下调乳腺癌HER-2的表达机制,为乳腺癌抗HER-2治疗提供新的实验依据。方法:利用HDAC抑制剂处理HER-2阳性乳腺细胞,q PCR和Western检测HER-2基因和蛋白水平的变化,同时采用mi RNA芯片筛选HDAC抑制剂相关的mi RNA谱,q PCR验证mi RNA表达变化。结果:体外细胞实验证实HDAC抑制剂TSA和SAHA可下调乳腺癌细胞系HER-2的表达,TSA可下调BT474的HER-2基因表达,浓度为100 nmol时下调10.7%,浓度为200 nmol时下调38.9%(P0.05)。TSA对原代细胞HER-2基因表达无明显下调(P0.05)。SAHA对BT474中HER-2基因表达的影响,浓度5μmol/L组下调93.9%(P0.05),而1μmol/L组无明显下调。SAHA对原代细胞HER-2基因表达下调较为明显,浓度1μmol/L时下调92.7%,浓度5μmol/L时下调87.1%。通过mi RNA芯片筛选出7条mi RNA,q PCR监测SAHA、TSA处理后,mi R-762基因表达上调2.11倍。结论:HDAC抑制剂可能通过mi RNA表达谱改变介导下调乳腺癌HER-2的表达。
[Abstract]:Aim: to investigate the mechanism of histone deacetylase (HDAC) inhibitor down-regulating the expression of HER-2 in breast cancer, and to provide a new experimental basis for anti-HER-2 therapy in breast cancer. Methods: HER-2 positive mammary gland cells were treated with HDAC inhibitors and the changes of HER-2 gene and protein were detected by Western blot. Results: HDAC inhibitor TSA and SAHA could down-regulate the expression of HER-2 gene in breast cancer cell line HER-2. TSA could down-regulate the expression of HER-2 gene in BT474 cell line. When the concentration was 100 nmol, the HER-2 gene expression was down-regulated by 38.9% (P0.05). TSA had no effect on the expression of HER-2 gene in BT474 cells (P0.05) .SAHA had no effect on the expression of HER-2 gene in BT474 cells. In 5 渭 mol / L group, 93.9% (P0.05) was down-regulated, while in 1 渭 mol / L group there was no obvious down-regulation of HER-2 gene expression in primary cells. The expression of HER-2 gene was down-regulated at 1 渭 mol / L and 87.1 渭 mol / L, respectively. Seven miRNA-qPCR fragments were screened by mi RNA microarray to detect the up-regulation of gene expression by 2.11 times after SAHAA TSA treatment. Conclusion the expression of HER-2 in breast cancer may be down-regulated by the alteration of mi RNA expression profile.
【作者单位】：天津医科大学肿瘤医院乳腺内科国家肿瘤临床医学研究中心乳腺癌防治教育部重点实验室;天津医科大学肿瘤医院Ⅰ期试验病房;天津医科大学肿瘤医院乳腺病理科;
【基金】：国家自然科学基金面上项目(编号:81472183) 国家科技支撑计划课题(编号:2015BAI12B15)资助~~
【分类号】：R737.9

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