Effects of the PARP inhibitor Niraparib on the radiosensitivity of human lung and cervical cancer cells

Abstract

Objective

To investigate the effect of Niraparib, a clinically approved PARP inhibitor on the radiosensitivity of human lung and cervical cancer cells, and preliminarily explore the underlying mechanism.

Methods

The human lung cancer cell line A549 and human cervical cancer cell line Siha were both treated with Niraparib for 1 ​h, or X-ray irradiation with 4 ​Gy, or Niraparib for 1 ​h combined with X-ray irradiation with 4 ​Gy. The effect was examined via measurements of cell proliferation by the cell counting kit-8 assay, and cell viability was detected by clone formation assays. Cell apoptosis and cell cycle distribution were investigated by flow cytometry.

Results

In human lung and cervical cancer cell lines, Niraparib combined with radiation therapy significantly inhibited cell proliferation. The proportion of apoptotic cells in cell lines treated with Niraparib plus radiation (the combination group) was significantly higher compared with control, radiation, and Niraparib groups (P ​< ​0.05). Additionally, the proportion of A549 ​cells in the G₂/M phase was significantly increased in the combination group compared with the radiation group (P ​< ​0.05).

Conclusion

PARP inhibitor Niraparib increases the radiosensitivity of tumorcells, promotes their apoptosis, and induces cell cycle redistribution. The possible mechanism is associated with the inhibition of radiation-induced DNA damage repair.