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