RNAi-mediated inhibition of PDGF-D leads to decreased cell growth, invasion and angiogenesis in the SGC-7901 gastric cancer xenograft model.
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.
Zhao
Lin
L
Department of Gastrointestinal Surgery, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Zhang
Caiquan
C
Liao
Gang
G
Long
Jiegen
J
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D034622:RNA Interference; D011897:Random Allocation; D013274:Stomach Neoplasms / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
D010982:Platelet-Derived Growth Factor