Journal
CANCER BIOLOGY & THERAPY
Volume 9, Issue 1, Pages 42-48Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.9.1.10282
Keywords
PDGF-D; RNA interference; gastric cancer; cell growth; invasion; angiogenesis
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Platelet-derived growth factor-D (PDGF-D) plays an important role in many types of human cancer. however, little is known about the function of this gene in gastric cancer. here we demonstrated that PDGF-D is commonly overexpressed in gastric cancer. silencing of PDGF-D using RNA interference significantly attenuated the proliferation and invasion potentials of sGC-7901 gastric cancer cells in which PDGF-D is overexpressed. Moreover, suppression of PDGF-D expression resulted in less activation of beta-catenin and its downstream effector genes, cyclin D1 and matrix metalloproteinases, which are known to be involved in cell proliferation and invasion, respectively. Further, downregulation of PDGF-D remarkably reduced VEGF expression and secretion and proangiogenic activities of sGC-7901 cells in vitro. Most importantly, PDGF-D downregulation caused a significant decrease in tumor growth and angiogenesis in a sGC-7901 xenograft model. Together these findings suggest that PDGF-D is involved in the promotion of gastric cancer growth, invasion and angiogenesis, and RNai-mediated silencing of this gene may thus offer a promising therapeutic strategy for PDGF-D-overexpressing gastric cancer.
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