CUDC-907 induces DNA damage and autophagy in glioma cells / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of CUDC-907, a dual histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K) inhibitor, on the DNA damage, cell cycle distribution and autophagy in human glioma U251cells.METHODS:U251 cells were treated with CUDC-907 of different concentrations, and the cell viability was detected by MTT assay.The quantitativeγ-H2AX foci were determined by laser scanning confocal microscopy.The cell cycle distribution of U251 cells was examined by flow cytometry.The protein expression was determined by Western blot analysis.RESULTS:CUDC-907 inhibited the cell viability and the phosphorylation of Akt and p70 ribosomal protein S6 kinase (p70s6K) in the U251 cells (P<0.05).In CUDC-907-treated cells, the number ofγ-H2AX foci and protein expression ofγ-H2AX were increased significantly (P<0.05).CUDC-907 also induced cell arrest in theM phase by up-regulating the expression of p21, and inhibiting the protein level of cyclin B1 and the phosphorylation of cell division cycle protein2 (Cdc2).In addition, CUDC-907 triggered cell autophagy, and inhibition of autophagy increased CUDC-907-induced DNA damage of U251 cells.CONCLUSION:CUDC-907 significantly inhibits PI3K/Akt signaling pathway, induces DNA damage and arrests cell cycle inM phase.Blockage of autophagy promotes CUDC-907-induced DNA damage of U251cells.