Affiliation:
1. Harbin Medical University Cancer Hospital
2. Gansu Province Maternal and Child Health Hospital
3. Beijing Center for Physical and Chemical Analysis
4. Harbin Wenkang Hospital
5. The Ninth People's Hospital of Dongguan City
Abstract
Abstract
Objective
Apatinib is a noval antiangiogenic agents, and it has great clinical benefit. Immunotherapy has a low response rate in patients with ovarian cancer, but combination with antiangiogenic therapy might improve the antitumour response. The aim of our study was to assess the expression of programmed cell death 1 ligand 1 (PD-L1) in vivo and in vitro and the potential effect of apatinib in combination with an anti-PD-1 antibody in mice with ovarian cancer.
Methods
We assessed the expression of PD-L1 in vivo and in vitro by real-time quantitative reverse transcription–polymerase chain reaction (qRT‒PCR), flow cytometry and western blotting in different concentrations. We constructed a xenograft model and measured mouse weight and tumour size after treatment. Tumour tissues from the mice were subjected to HE staining, and we detected Ki-67, CD4 and CD8 expression by immunohistochemical staining (IHC).
Results
Apatinib monotherapy increased the expression of PD-L1 by dose-dependent, as determined by qRT‒PCR, flow cytometry, and western blotting in vivo and in vitro. Apatinib combined with an anti-PD-1 antibody had the most pronounced antitumour effect on ovarian cancer among the combination treatment and the two monotherapies. The most obvious changes were a decrease in Ki-67 expression and increases in CD4 and CD8 expression.
Conclusions
Our study showed that apatinib upregulates the expression of PD-L1 to exert antitumour effects. Apatinib in combination with an anti-PD-1 antibody led to a remarkable reduction in tumour growth, providing evidence for clinical trials.
Publisher
Research Square Platform LLC