Cyclooxygenase-2 inhibitors suppress angiogenesis and growth of gastric cancer xenografts.
Many researches have confirmed the tumor-prophylactic effects of cyclooxygenase-2 (COX-2) inhibitors. We previously observed their anti-cancer effects in vivo in nude mice and found that sulindac, a traditional non-steroidal anti-inflammatory drug (NSAID), and celecoxib, a selective COX-2 inhibitor, depressed the growth of SGC7901 xenografts via altering cell kinetics. Then we deeply studied the relationship between the two drugs and angiogenesis in gastric cancer. The results showed both sulindac and celecoxib decreased the micro-vessel density (MVD), which was labeled by either CD34 or VWF staining, within xenografts. Expression of both vascular endothelial growth factor (VEGF) and FGF-1 was suppressed. In addition, a positive correlation between MVD and the volume of SGC7901 xenografts was found. The effect of selective COX-2 inhibitor was stronger than non-special one despite of the insignificant difference. These results demonstrate that COX-2 plays an important role in angiogenesis of cancer. Apart from interfering cell kinetics, decreasing the expression of angiogenic factors and then inhibiting tumor angiogenesis could also be one of the mechanisms that COX-2 inhibitors suppress the growth of gastric cancer. These findings offer another theory basis for the future clinical application of NSAIDs against cancer.
Wu
Y-L
YL
Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, China.
Fu
S-L
SL
Zhang
Y-P
YP
Qiao
M-M
MM
Chen
Y
Y
D020533:Angiogenesis Inhibitors; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology*; D012039:Regional Blood Flow / Q000502:physiology; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016220:Fibroblast Growth Factor 1; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2