Abstract:  Objective To investigate the effect of Apatinib on the radiosensitivity of gastric cancer HGC-27 cells and its possible mechanism. Methods HGC-27 cells were treated with different concentrations of Apatinib (5 μmol/L, 10 μmol/L, 15 μmol/L, 20 μmol/L) and different irradiation doses (2 Gy, 4 Gy, 6 Gy, 10 Gy, 20 Gy). HGC-27 cells were then irradiated with 2 Gy and 6 Gy alone or combined with 10 μmol/L Apatinib. The expression of vascular endothelial growth factor （VEGF） was detected by ELISA, cell proli-feration capacity was detected by CCK-8, cell apoptosis and cell cycle were detected by flow cytometry, and expression of γ-H2AX was detected by immunofluorescence staining. Results Apatinib inhibited the proliferation of gastric cancer HGC-27 cells in a concentration- and time-dependent manner (all P<0.05). Different doses of irradiation promoted the release of VEGF in a time-and dose-dependent manner (all P<0.01). After the combination of 10 μmol/L Apatinib with 2 Gy and 6 Gy irradiation, respectively, the inhibition of cell proliferation, apoptosis rate and proportion of cells in G2/M phase of HGC-27 cells were increased compared with those in the single irradia-tion group (all P<0.01). The effect intensity of 6 Gy combined group was greater than that of 2 Gy combined group (all P<0.01). The nucleus focal quenching of γ-H2AX in the 6 Gy combined group was delayed compared with that in the 6 Gy single irradiation group. Conclusions Apatinib enhances the radiosensitivity of gastric cancer HGC-27 cells by inhibiting cell proliferation, promoting cell apoptosis and inducing cell cycle redistribution. The underlying mechanism may be related to the delay of γ-H2AX expression and the interference of DNA double-strand fracture repair.

Key words:  Gastric cancer, Vascular endothelial growth factor, Apatinib, Radiosensitivity