Metronomic docetaxel chemotherapy inhibits angiogenesis and tumor growth in a gastric cancer model

Low-dose metronomic (LDM) chemotherapy represents a new strategy to treat solid tumors by stronger antiangiogenic activity and less side effects. The aim of the study is to rationally develop a docetaxel metronomic regimen in preclinical settings of gastric cancer. In vitro cell proliferation, apoptosis, and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on human umbilical vein endothelial cells (HUVECs) and gastric cancer (BGC-823) cells exposed for 144 h to metronomic concentrations of docetaxel. BGC-823 human gastric cancer xenograft model was used, and tumor growth and side effects were closely monitored. Quantitative real-time PCR was used to determine TSP-1/VEGF mRNA levels in tumor samples. Expression of VEGF and CD31 was observed by immunohistochemistry. Our results indicated that LDM docetaxel preferentially inhibited HUVEC cell proliferation and induced HUVEC apoptosis. Docetaxel significantly increased TSP-1 expression and secretion in HUVEC cells whereas the expression and secretion of VEGF significantly decreased in BGC-823 cells. LDM docetaxel significantly inhibited BGC-823 tumor growth in the absence of toxicity, which was accompanied by decreases in microvessel density (MVD) and VEGF and increases in TSP-1 gene expression in tumor tissues. In vitro results show the antiangiogenic properties of LDM docetaxel. In vivo, LDM docetaxel treatment is effective against gastric tumor and microvessel growth without toxic effect on nude mice.