Capecitabine combined with (-)-epigallocatechin-3-gallate inhibits angiogenesis and tumor growth in nude mice with gastric cancer xenografts

Abstract

Low-dose metronomic chemotherapy represents a new strategy to treat solid tumors by exhibiting stronger anti-angiogenic activity and less side effects, especially in combination with other anti-angiogenic agents. Capecitabine is a novel fluoropyrimidine carbamate, which has a broader spectrum of antitumor activity than other fluoropyrimidines, such as 5-FU, DFUR or UFT; it has proved effective over a wide dose range. The aim of this study was to investigate the anti-angiogenic effect of capecitabine alone and combined with the angiogenic inhibitor (-)-epigallocatechin-3-gallate (EGCG) on gastric cancer. A BGC-823 human gastric cancer xenograft model was used, and tumor growth, side effects and the number of days of survival of mice were closely monitored and recorded. Quantitative real-time PCR was used to determine vascular endothelial growth factor (VEGF) mRNA levels. The expression of VEGF and CD31 was determined by immunohistochemistry. Our results indicated that metronomic capecitabine inhibited angiogenesis, growth of gastric cancer and improved survival with less toxicity, and the effects were further enhanced by the concurrent administration of EGCG. Clinical trials and further pre-clinical studies, will hopefully provide answers to the use of continuous low-dose anti-angiogenic therapies for the treatment of human gastric cancer.