Apatinib enhances the antitumor effects of radiation in HeLa cell line mouse model of invasive cervical cancer

BACKGROUND: There is the lack of reports on apatinib (APA) combined with radiation in the treatment of cervical cancer. The aim of our study was to investigate the anti-tumor effect of APA combined with radiation using an in vivo model of cervical cancer. METHODS: The mouse models, established using Henrietta Lacks (HeLa) cells, were randomly divided into 4 groups: the control group, radiotherapy (RT) alone group, cisplatin (DDPs) combination RT group (DDPs + RT), and APA combination RT group (APA + RT). The expressions of the vascular endothelial growth factor receptor-2 (VEGFR-2), platelet endothelial cell adhesion molecule-1 (CD31), proliferating cell nuclear antigen (Ki-67), and histone H2AX family member (γ-H2AX) were determined using immunohistochemistry (IHC), the extent of apoptosis was determined using terminal deoxynucleotidyl transferase (TdT)-mediated (dUTP) nick-end labeling (TUNEL), and tumor metabolism was determined using micro18F-fluorodexyglucose positron emission tomography/computed tomography. The length of survival was observed and recorded. RESULTS: The positive expressions of VEGFR-2, CD31, and Ki-67 in the APA + RT group were obviously reduced compared with the control, RT, and DDPs + RT groups (P<0.05). The positive expression of γ-H2AX was obviously increased compared with the control and RT groups (P<0.05), whereas the apoptosis rate in the APA + RT group was obviously increased compared with the control, RT, and DDPs + RT groups (P<0.05). The tumor metabolism and volume in the APA + RT group were obviously reduced compared with the control, RT, and DDPs + RT groups. The length of survival was prolonged by 22 and 11 days in the APA + RT group compared with the RT and DDPs + RT groups, respectively (P<0.05). CONCLUSIONS: The combination of APA and RT could significantly enhance the anti-tumor efficacy of RT and prolong the median survival in a mouse model of cervical cancer.