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Effect of Ape1/Ref-1 on injury caused by stereotactic ablative radiotherapy in the treatment of early stage non-small cell lung cancer

Lei Han, Renzhi Yu, Xin Ni, Zenglei Zhang

Objective: To explore the effect of Ape1/Ref-1 on injury caused by stereotactic ablative radiotherapy in the treatment of early stage non-small cell lung cancer.

Method: Human lung cancer cell line A549 cells or irradiated A549 cells, which received 8 MV X ray radiation exposure were treated with different concentrations of genistein (30, 60, and 90 μM) for 1, 2, or 3 d. Western blot was used to measure the expression levels of Ape1/Ref-1 and p53. Luciferase reporter gene assay was used to measure the relationship between p53 and Ape1/Ref-1.

Results: Genistein suppressed the expression of Ape1/Ref-1 in A549 cells in a time- and dose-dependent manner. In contrast, genistein increased the expression of p53 in A549 cells in a time- and dosedependent manner. Irradiation of cells further suppressed the expression of Ape1/Ref-1 in A549 cells and increased the expression of p53 in A549 cells. Stereotactic Ablative Radiotherapy (SABR) in combination with genistein not only reduced the expression levels of Ape1/Ref-1, but also increased the expression of p53. Moreover, p53 reduced the transcriptional activity of Ape1/Ref-1 promoter.

Conclusion: SABR in combination with genistein increased the expression of p53 in A549 cells, leading to down regulation of Ape1/Ref-1. This study indicated that SABR in combination with genistein might be of great significance in the treatment of early stage Non-Small Cell Lung Cancer (NSCLC).