国际肿瘤学杂志

国际肿瘤学杂志 ›› 2015, Vol. 42 ›› Issue (8): 561-565.doi: 10.3760/cma.j.issn.1673422X.2015.08.001

• 论著 •    下一篇

组蛋白去乙酰化酶抑制剂SNDX275对乳腺癌BT474细胞增殖抑制作用

尹江,刘浩,邓敏,贺智敏   

  1. 510095广州医科大学附属肿瘤医院肿瘤研究所
  • 出版日期:2015-08-08 发布日期:2015-06-29
  • 通讯作者: 刘浩，Email：haoliu2020@163.com E-mail:haoliu2020@163.com
  • 基金资助:

    国家自然科学基金（81472763）；广州市科技计划项目（2014J4100061）

The effect of HDAC inhibitor SNDX275 on inhibiting breast cancer BT474 cell proliferation

Yin Jiang, Liu Hao, Deng Min, He Zhimin   

  1. The effect of HDAC inhibitor SNDX275 on inhibiting breast cancer BT474 cell proliferation
  • Online:2015-08-08 Published:2015-06-29
  • Contact: 刘浩 E-mail:haoliu2020@163.com

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摘要： 目的明确组蛋白去乙酰化酶抑制剂SNDX275对ErbB2阳性乳腺癌BT474细胞的增殖抑制作用及其机制。方法以磷酸盐缓冲液（PBS）处理的BT474细胞作为对照组、SNDX275处理的BT474细胞作为实验组，使用终浓度为0、0.5、1.0、2.0、3.0、4.0 μmol/L的SNDX275处理细胞，利用MTS实验、克隆形成实验检测细胞增殖能力。采用Western blotting实验检测ErbB2、ErbB3、pAkt的蛋白表达，实时荧光定量PCR检测miR125a、miR125b的表达。MTS实验检测SNDX275对转染miR125抑制剂的乳腺癌BT474细胞的增殖抑制作用。结果MTS实验检测结果发现SNDX275能明显抑制细胞的增殖且具有浓度依赖性，4.0 μmol/L的SNDX275对细胞的抑制率约(68.00±4.45)%。平板克隆实验结果表明，SNDX275能明显抑制乳腺癌BT474细胞克隆的形成。Western blotting结果显示SNDX275明显抑制ErbB2、ErbB3、pAKT的表达。实时荧光定量PCR分析发现，与PBS处理的BT474细胞对比，2 μmol/LSNDX275 BT474细胞分别上调miR125a、miR125b约3.22±1.17倍、5.42±0.38倍，差异均具有统计学意义（t=4.338,P=0.049；t=21.805,P=0.002）。MTS实验结果显示，与PBS对照组相比，SNDX275组和转染miR125抑制剂组对乳腺癌细胞BT474的抑制率分别为（56.97±3.56）%、（10.67±2.21）%，两组之间差异具有统计学意义（t=-10.993，P=0.008）。结论SNDX275通过上调miR125a、miR125b抑制ErbB2ErbB3Akt信号通路，进而抑制ErbB2阳性乳腺癌BT474细胞的增殖。

关键词: 乳腺肿瘤, 细胞增殖, 微RNAs

Abstract: The effect of HDAC inhibitor SNDX275 on inhibiting breast cancer BT474 cell proliferationYin Jiang, Liu Hao, Deng Min, He Zhimin. Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095, China Corresponding author: Liu Hao, Email: haoliu2020@163.com【Abstract】ObjectiveTo explore the effect and molecular mechanism of HDAC inhibitor SNDX275 inhibiting cell proliferation in ErbB2overexpressing breast cancer BT474 cells.  MethodsBreast cancer BT474 cells were treated with HDAC inhibitor SNDX275, setting as test group, and the cell line treated with phosphate buffered saline (PBS) as control. The concentration of SNDX275 were 0, 0.5, 1.0, 2.0, 3.0, 4.0 μmol/L respectively. Cell proliferation was analyzed by MTS assay and colony formation assay, the expressions of ErbB2, ErbB3, pAkt were analyzed by Western blotting, and the expressions of miR125a, miR125b were analyzed by RTPCR. After transfecting miRNA125 inhibitor into BT474 cells, the inhibition rate of SNDX275 was tested by MTS assay . ResultsMTS result showed that SNDX275 inhibited cell proliferation in BT474 cells in a dosedependent manner. The inhibition rate of 4.0 μmol/L SNDX275 was about (68.00±4.45)%. Clone assay indicated SNDX275 could inhibit the proliferation of BT474 cells. Western blotting result indicated that SNDX275 significantly inhibited the protein expressions of ErbB2, ErbB3 and pAkt, RTPCR result illustrated 2 μmol/L SNDX275 could increase the expressions of miR125a and miR125b about 3.22±1.17, 5.42±0.38 times compared with the PBS control respectively, the difference has a statistical significance (t=4.338，P=0.049; t=21.805，P=0.002). MTS result indicated that compared with the PBS control, the inhibition rate of SNDX275 group was （56.97±3.56）%， while the inhibition rate of SNDX275 and miRNA125 inhibitor group was (10.67±2.21）%， with a statistical significance（t=-10.993，P=0.008）.  ConclusionSNDX275 could inhibit cell proliferation of ErbB2overexpressing breast cancer BT474 cells, by inhibiting ErbB2ErbB3Akt signal pathway through upregulating miR125a and miR125b.

Key words: Breast neoplasms, Cell proliferation, MicroRNAs