The effect of apatinib combined with chemotherapy or targeted therapy on non-small cell lung cancer in vitro and vivo

Abstract

Background: The aim of this study was to investigate the feasibility of using a combination of apatinib in the treatment of non-small cell lung cancer. Apatinib is a tyrosine kinase inhibitor which selectivelyacts on vascular endothelial growth factor receptor 2 (VEGFR-2) and has shown good efficacy in a variety of malignancies, but the drug resistance is fast in single drug therapy. Methods: The inhibitory effect of apatinib and other drugs on lung cancer cells was determined by CCK-8 test in vitro, and the IC50 value was determined. To establish a nude mouse xenograft model, observe the inhibitory effect of apatinib combined with other drugs on lung cancer xenografts in nude mice; immunohistochemical staining of tumor microvessel density and Ki67 expression in transplanted tumor tissues; Western blot analysis of related signaling pathways expression; immunohistochemistry was used to detect tumor microvessel density in other organs and to observe its safety. Results: In this study, we found apatinib combined with pemetrexed, the first and third generation of epidermal growth factor receptor tyrosine kinase inhibitor, could synergistically inhibit the proliferation of non-small cell lung cancer cell (NSCLC) lines, reduce the microvessel density and Ki67 protein levels of three non-small cell lung cancer xenografts, and enhance anti-tumor activity by synergistically inhibiting the MAPK-ERK and PI3K-AKT-mTOR signaling pathway. Furthermore, there were no pathological abnormalities in the heart, brain, liver and kidney of each group. Conclusions: The efficacy of apatinib combination is better than that of monotherapy, and there is no significant difference in toxicity of important organs, which suggests the feasibility of a combination of apatinib in the treatment of non-small cell lung cancer.