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

Yun Wang; Li Zhang; Wei Liu; Jing-Pin Yang; Hong-Ju Peng; Jian-Wen Zhang

doi:10.21037/atm-22-1442

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

Ann Transl Med. 2022 Apr;10(8):459. doi: 10.21037/atm-22-1442.

Authors

Yun Wang^#¹, Li Zhang^#¹, Wei Liu^#², Jing-Pin Yang³, Hong-Ju Peng⁴, Jian-Wen Zhang^{1

5

6}

Affiliations

¹ Department of Oncology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
² Department of Oncology, People's Hospital of Dazu District, Chongqing, China.
³ Department of Oncology, the First Hospital of Guangyuan, Guangyuan, China.
⁴ Department of Oncology, Second People's Hospital of Neijiang, Neijiang, China.
⁵ Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China.
⁶ Academician (Expert) Workstation of Sichuan Province, Luzhou, China.

^# Contributed equally.

Abstract

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.

Keywords: Antiangiogenic therapy; apatinib (APA); cervical cancer; cisplatin (DDP); radiotherapy (RT).