Apatinib increases radiosensitivity of gastric cancer by inhibiting VEGF pathway / 中国病理生理杂志

ABSTRACT

AIM:To investigate radiosensitization effect of apatinib, a vascular endothelial growth factor (VEGF) receptor2 tyrosine kinase inhibitor, on human gastric carcinoma cell line SGC-7901 and its mechanism.METHODS:SGC-7901 cells were divided into control group, apatinib group, radiotherapy group and combination group.The cell viability was measured by CCK-8 assay.The changes of cell apoptosis and cell cycle were analyzed by flow cytometry.The protein levels of cell apoptosis biomarkers, such as PARP, cleaved caspase-9, cleaved caspase-3 and Bcl-2, and cell proliferation biomarkers, p-PLCγ1 and p-ERK1/2, were detected by Western blot.γ-H2AX expression was detected by immunofluorescence.RESULTS:Compared with apatinib group and radiation group, the cell viability was inhibited after treatment with both apatinib and X-ray (P<0.01).The protein levels of cell proliferation markers p-PLCγ1 and p-ERK1/2 were down-regulated.The cell apoptosis was enhanced (P<0.01).The protein levels of cell apoptosis makers such as PARP, cleaved caspase-9 and cleaved caspase-3 were up-regulated, while Bcl-2 was down-regulated.The disappearance of γ-H2AX foci in the nucleus was delayed, indicating that apatinib impaired the repair of radiation-induced DNA double-strand breaks.The proportion of G2 phase was significantly increased (P<0.01).The combination treatment had more significant effect on SGC-7901 cells than treating with apatinib or radiotherapy alone.CONCLUSION:Apatinib increases the radiosensitivity of gastric cancer cells via blocking VEGF pathway.