关键词: 阿帕替尼, 紫杉醇, 胃癌, PDX模型, 微血管密度

Abstract: Objective To investigate the predictive biomarker of efficacy of apatinib and its feasibility in combination with paclitaxel on patient-derived xenografts (PDX) for gastric cancer (GC). Methods A total of six GC PDX mouse models were selected. Each model was divided into control group, apatinib group, paclitaxel group and combination group. The tumor volume and the body weight of mice were measured and the tumor growth inhibition (TGI) rate was calculated. Targeted next-generation sequencing and transcriptome sequencing were conducted on tumor tissues of PDX models, respectively. The CD31 expressions of tumor tissues were detected by immunohistochemistry (IHC) assay. Results Apatinib monotherapy showed selective antitumor activities on six GC PDX models，which was superior to paclitaxel. After apatinib treatment, the expressions of FGFR1/2 were downregulated. The differentially expressed genes were significantly enriched in biological processes of vasculature development, blood circulation, inflammation response, and protein cascade activation and the complement and coagulation cascade signaling pathway. PDX models with relatively high microvessel density were more sensitive to apatinib than that of models with lower microvessel density. Conclusions Apatinib exerted its antitumor effect by inhibiting angiogenesis in GC PDX models. The microvessel density of tumor tissue might predict the efficacy of apatinib, and whether the combination of apatinib and paclitaxel should be recommended in clinical practice needs further validation.

Key words: apatinib, paclitaxel, gastric cancer, patient-derived xenografts, microvessel density