Abstract
Gastric cancer (GC) is the third leading cause of cancer-associated mortality globally. Although the diagnosis and therapeutic strategies for GC have improved, the prognosis for advanced gastric cancer (AGC) remains poor. Hence, the present study sought to design a zebrafish model established by microinjecting human MGC-803 GC cell line for studying personalized molecular-targeted cancer therapy. Apatinib, a novel molecular-targeted agent, was evaluated for its in vivo efficacy through a comparison among the control groups (no treatment) and subject groups (treatment). Newly formed vessel length and tumor volume were measured in all of the groups for further study. The length of newly formed vessels was obviously shortened after apatinib treatment in the zebrafish model established in this study. Meanwhile, apatinib exhibited the best antitumor growth effect with dose and time dependence by suppressing AKT/GSK3α/β signaling, which may be the mechanism underlying the profound antitumor clinical effect of apatinib. The data indicated that apatinib therapy exerts an anti-angiogenesis effect and it can be recommended as a proper antitumor growth therapy for GC patients. Additionally, zebrafish models could be designed as a potential practical tool to explore new anti-GC cancer drugs.
Highlights
Gastric cancer (GC) is the third leading cause of cancerassociated mortality globally and approximately 90% of GCs are diagnosed as adenocarcinoma, presenting a high mortality rate [1]
The results show that apatinib could not inhibit the proliferation of GC cells in the in vitro experiments, especially in HGC-27 and BGC-823 cell lines
Previous research has found that AKT/GSK-3β/βcatenin signaling is crucial for the proliferation and invasion of gastric cancer cells [21]
Summary
Gastric cancer (GC) is the third leading cause of cancerassociated mortality globally and approximately 90% of GCs are diagnosed as adenocarcinoma, presenting a high mortality rate [1]. The application of molecular-targeted anticancer drugs (e.g., trastuzumab and apatinib) provides a promising optional therapy for GC, especially AGC [6]. Known as YN968D1 (molecular weight 493.58 Da), is one of the most efficient oral anticancer agents, verified by preclinical and clinical trials for the treatment of various solid malignancies [7,8,9]. This novel small-molecule drug targets angiogenesis by selective inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) and it can partly inhibit cKit and c-Src tyrosine kinases [10]. There are no practical biomarkers that can hint toward the most significant application of apatinib in GC patients during clinical practice
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