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  • Title: Metronomic docetaxel chemotherapy inhibits angiogenesis and tumor growth in a gastric cancer model.
    Author: Wu H, Xin Y, Zhao J, Sun D, Li W, Hu Y, Wang S.
    Journal: Cancer Chemother Pharmacol; 2011 Oct; 68(4):879-87. PubMed ID: 21290245.
    Abstract:
    PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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