Roles of DNA polymerase ζ in the radiotherapy sensitivity and oxidative stress of lung cancer cells

Abstract

Background: Previous reports stated that DNA polymerase ζ is highly expressed in lung cancer tissues. The present study aimed to investigate the roles and underlying mechanism of DNA polymerase ζ in lung cancer cell radioresistance.

Methods: The A549 and HCC827 cells were used to evaluate the effects of different doses of radiation on the mRNA and protein expressions of DNA polymerase ζ. Multiple assays, including PCR, western blot, flow cytometry, and EdU have been used to investigate the roles of DNA polymerase ζ on the cellular behaviors of A549 and HCC827 cells.

Results: The mRNA and protein expression of REV7L in A549 and HCC827 cells were significantly increased after 6 Gy irradiation compared to the control group. In A549 and HCC827 cells, over-expression of polymerase ζ decreased the radiosensitivity, inhibited cell apoptosis as well as reduced oxidative stress; while the knockdown of polymerase ζ showed the opposite effects. Knockdown of Polymerase ζ in xenograft animal models significantly decreased tumor size and induced oxidative stress of tumor tissues after irradiation.

Discussion: Our results provided a theoretical basis for targeting DNA polymerase ζ to improve the radiosensitivity of the lung cancer cells to radiotherapy.

Keywords: DNA polymerase; Lung cancer; Oxidative stress; Radioresistance.