Inhibitory effects of icotinib combined with antiangiogenic drugs in human non‐small cell lung cancer xenograft models are better than single target drugs

Abstract

Abstract Background This study aimed to evaluate the inhibitory effects and potential mechanisms of icotinib combined with antiangiogenic drugs on lung adenocarcinoma in vivo. Methods A total of 72 mouse xenograft models established with human lung adenocarcinoma cells (HCC827) were randomly divided into six groups, including control, icotinib (Ic), bevacizumab (Bev), recombinant human endostatin (En), Ic + Bev and Ic + En groups. Mouse weights and tumor volumes were measured regularly. Half of the nude mice in each group were sacrificed after 16 days of drug treatment. The remaining animals were observed for another 16 days without drug supply. Immunohistochemical staining was performed to detect microvessel density in tumor heart, liver, brain specimens from the nude mice and Ki67 expression. Differential expression of vascular endothelial growth factor (VEGFA) in tumor tissue specimens was determined by ELISA and Western blot. Results The results showed that the combined drugs inhibited tumor growth more substantially compared with single drugs, without increasing the toxic effects. The antiangiogenesis effect of the combination was better than that of single drug treatment. In addition, both types of targeted drugs and combination medication not only significantly reduced microvessel density in the tumor tissue itself, but also had a certain impact on decreasing microvessel density in the liver. The combination decreased VEGFA and Ki‐67 amounts significantly more than icotinib or endostatin as a monotherapy. Conclusions Icotinib combined with bevacizumab or rh‐endostatin has a stronger inhibitory effect on tumor growth than single‐target drug in vivo, with no additional side effects.

Keywords

• bevacizumab
• icotinib
• microvessel density
• recombinant human endostatin (rh‐endostatin)
• vascular endothelial growth factor A (VEGFA)