Abstract
BackgroundGastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored areas of precision medicine. In this study, we aimed to establish an in vivo patient-derived xenograft (PDX) model based on zebrafish (Danio rerio) embryos, allowing for a rapid analysis of the angiogenic and invasive potentials, as well as a fast drug sensitivity testing.MethodsTwo human gastric cancer cell lines (AGS and SGC-7901) were xenografted into zebrafish embryos, their sensitivity to 5-FU were tested both in vitro and in vivo. Fourteen human primary cells from gastric cancer tissue were xenografted into zebrafish embryos, their proliferating, angiogenic and metastatic activities were evaluated in vivo. Sensitivity to 5-FU, docetaxel, and apatinib were also tested on primary samples from four patients.ResultsSGC-7901 showed higher sensitivity to 5-FU than AGS both in vitro (6.3 ± 0.9 μM vs.10.5 ± 1.8 μM) and in vivo. Nine out of fourteen patient samples were successfully transplanted in zebrafish embryos and all showed proliferating, angiogenic and metastatic potentials in the living embryos. Four cases showed varied sensitivity to the selected three chemotherapeutic drugs.ConclusionsOur zebrafish PDX (zPDX) model is a preclinically reliable in vivo model for GC. The zPDX model is also a promising platform for the translational research and personalized treatment on GC.
Highlights
Gastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China
The median survival rate of patients with advanced GC is still less than 12 months, and the overall 5-year survival rate of GC is as low as only 20%, these are due to the chemoinsensitivity or chemoresistance of GC resulting from the high heterogeneous nature and other unknown mechanisms [4]
At a 72 h-incubation time, the half maximal inhibitory concentration (IC50) were 10.5 ± 1.8 μM and 6.3 ± 0.9 μM for AGS and SGC-7901 respectively (Table 1), in which SGC-7901 showed higher sensitivity to 5-FU treatment compared to AGS in vitro
Summary
Gastric cancer (GC) is among the most commonly cancer occurred in Asian, especially in China. With its high heterogeneity and few of validated drug targets, GC remains to be one of the most under explored areas of precision medicine. According to the 2012 statistics of the International Agency for Research on Cancer (IARC), GC was the fifth most common malignancy and the third leading cause of cancer death worldwide [1]. 2nd and 3rd commonly diagnosed cancers among men and women respectively, and was the 2nd leading causes of cancer death among both sexes [2]. In China, nearly 90% of patients were diagnosed as advanced gastric cancer [3]. The addition of targeted drugs has improved the prognosis to some extent in recent years, the comprehensive treatment based on fluorouracil containing chemotherapy remains the main strategy for advanced GC. Development of new drugs, as well as establishment of personalized treatment strategies for current drugs becomes the principal challenges
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