ZEB1 regulates the radiosensitivity of gastric cancer cell AGS by up-regulating ATM expression / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the effect of Zinc finger E-box binding homeobox protein 1 (ZEB1) on the radiosensitivity of gastric cancer cells AGS and its possible mechanism. Methods AGS cells were irradiated by X-rays at different doses (0, 2, 4, 6, and 8 Gy). Western blot was used to observe the expression of ZEB1 in cells. AGS cells, in logarithmic growth phase, were transfected with of ZEB1 gene or its interference plasmids, the corresponding control plasmids ( pcDNA3. 1 ) and negative control interference plasmids. They were classified as overexpression ZEB1 group, silencing ZEB1 group, control group and negative control group, respectively. The effect of overexpression and silencing ZEB1 on the survival of AGS cells after irradiation were analyzed by colony formation assay. The cell apoptosis rate was analyzed by flow cytometry. The expressions of histone H2A (H2AX), phosphorylated H2AX (γ-H2AX) and telangiectasia mutated gene (ATM) were detected by Western blot. Results The expression of ZEB1 in AGS cells was dependent on radiation dose (F=58. 57, P<0. 05). Overexpression of ZEB1 increased AGS cells viability, inhibitedγ-H2AX expression (t=12. 18, P<0. 05), blocked cell apoptosis (t=7. 27, P<0. 05) and up-regulated ATM expression in time-dependent manner after irradaition (F=165. 70, P <0. 05). Silencing ZEB1 reduced AGS cells viability, increased γ-H2AX expression ( t =12. 88, P<0. 05) and cell apoptosis (t =8. 36, P <0. 05), and down-regulated of ATM expression (F=44. 80, P<0. 05). Conclusions ZEB1 regulates the radiosensitivity of gastric cancer AGS cells by up-regulating ATM expression.