Abstract:

Objective To discuss the synergistic inhibitory effect of apatinib mesylate （apatinib） combined with radiotherapy （RT） on the hepatocellular carcinoma （HepG2） cells in vitro， and to clarify its related antitumor mechanism. Methods The HepG2 cells were cultured in vitro and treated with different concentrations of apatinib and/or varying doses of X-rays. MTT method was used to detect the survival rates of the cells in various groups； the inhibitory rates of cell proliferation and the 20% inhibitory concentration （IC₂₀） of apatinib were calculated； the X-ray irradiation dose for subsequent experiments was detected. The HepG2 cells were divided into apatinib group， RT group， and apatinib+RT group （combined group）. Flow cytometry was used to detect the apoptotic rates of the cells in various groups； wound healing assay was used to detect the migration rates of the cells in various groups； ELISA method was used to detect the levels of vascular endothelial growth factor （VEGF） in the cell culture supernatant in various groups. Results The MTT results showed that the IC₂₀ of apatinib was 1.32 μmol·L^-1， and this concentration was used for subsequent experiments， and the X-ray irradiation dose for the follow-up experiments was 2 Gy. Compared with control group， the apoptotic rates of the cells in apatinib group and RT group had no significant differences （P>0.05）， while the apoptotic rate of the cells in combined group was increased （P<0.05）. Compared with control group， the migration rates of the cells in apatinib group， RT group， and combined group were decreased （P<0.05）； compared with apatinib group and RT group， the migration rate of the cells in combined group was decreased （P<0.05）. Compared with control group， the levels of VEGF in the cell culture supernatant in apatinib group and combined group were decreased （P<0.05）； compared with apatinib and RT group， the level of VEGF in the cell culture supernatant in combined group was decreased （P<0.05）. Conclusion Apatinib combined with radiotherapy significantly inhibits the proliferation and migration of the HepG2 cells in vitro and induces the apoptosis； its effect may be related to the inhibition of VEGF secretion by cells.

Key words: Hepatocellular carcinoma, Apatinib mesylate, Radiotherapy, Cell proliferation, Apoptosis, Cell migration, Vascular endothelial growth factor