Abstract: Objective : To observe the effect of tyrosine kinase inhibitor AG825 on the radiosensitivity and prolifera-tion of a breast cancer cell line with high expression of ERBB2, and to explore its involvement in the repair ofDNA double strand breaks and the expression of DNA-PKcs protein. Methods : MTT assay was used to ob-serve the inhibitory effect of different concentrations (0, 2, 5, 10, 20, 50, 100μM) of AG825 on the proliferationof breast cancer cell line MDA-MB-453. The cells were divided into 3 groups: the control group, the radiationgroup, and the radiation plus AG825 group. We used clone formation assay to analyze the survival fractionsafter radiation in the three groups. Single cell neutral gel electrophoresis (comet assay) was used to detectDNA double strand breaks and Western blot was applied to detect the expression of DNA-PKcs protein. Re-sults : MTT assay showed that AG825 decreased the proliferation of MDA-MB-453 cells in a dose dependentmanner. Survival fractions of the radiation group were significantly lower than in the control group, and sur-vival fractions of the radiation plus AG825 group were lower than that of the radiation group. In the comet as-say, tail moment of the radiation group was higher than that of the control group. The radiation plus AG825group had a higher tail moment than the radiation group. Western blot showed that at different time points af-ter irradiation, the expression of DNA-PKcs protein in the radiation plus AG825 group was lower than in the ra-diation group. Conclusion : AG825 can inhibit the proliferation of breast cancer cells with high expression ofERBB2. AG825 can increase the radiosensitivity of breast cancer cell line MDA-MB-453, and the mechanismmay involve AG825 inhibiting the expression of DNA-PKcs and thus decreasing the post-irradiation repair ofDNA double strand breaks.