Targeting Ku86 enhances X-ray-induced radiotherapy sensitivity in serous ovarian cancer cells

Drug resistance and recurrence are significant contributors to the poor prognosis of serous ovarian cancer (SOC). Radiotherapy is primarily used for the treatment of cancer recurrence; however, it is rarely applied in cases of SOC. Ku86, also known as XRCC5(X-ray repair cross complementing 5), has rarely been reported in the radiotherapy of SOC. Therefore, this study aimed to investigate the role of Ku86 in the development of SOC and in radiotherapy sensitivity induced by X-ray. In vitro experiments and database analysis showed significantly elevated expression of Ku86 in SOC. Further, after down-regulating Ku86 using RNAi technology, cell proliferation was inhibited. Further, the cell cycle was blocked in the G2 phase, and G2/G1 was increased since X-ray irradiation led to an increase in γ-H2AX. Down-regulation of Ku86 in the case of X-ray irradiation will promote the above biological effects, with more γ-H2AX and higher G2/G1. Here, we further deduce that Ku86 promotes the X-ray induced effect is most likely to activate the ATR pathway to block the cell cycle while inhibiting the NHEJ pathway to inhibit DNA damage response(DDR). Together these findings suggest that the down-regulation of Ku86 can improve X-ray-induced radiotherapy by affecting ATR and NHEJ pathways, and provide a new strategy for the treatment of ovarian cancer.