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

Abstract

BackgroundThere 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.MethodsThe 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.ResultsThe 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).ConclusionsThe 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.