[Effects of rofecoxib on angiogenesis of pancreatic cancer xenograft in nude mice].
OBJECTIVE
Angiogenesis plays a crucial role in invasive tumor growth. Overexpressed cyclooxygenases-2 (COX-2) may be related to increased angiogenesis in the rapidly progressed tumor. The purpose of the present study was to investigate the effects of the highly selective COX-2 inhibitor,rofecoxib on the growth of pancreatic cancer xenografts in nude mice in vivo as well as on tumor-associated angiogenesis.


METHODS
BXPC-3 human pancreatic cancer cells overexpressing COX-2 was inoculated subcutaneously into nude mice. Rofecoxib (30 mg/kg) was administered orally to animals every day for eight weeks. The microvessel density was immunostained with factor VIII antibody. The expression of VEGF on BXPC-3 pancreatic cancer cell line was measured by immunocytochemistry in vitro. Gelatin zymography and RT-PCR technology were used to determine MMP-2 progelatinase and expression of MMP-2 mRNA.


RESULTS
Rofecoxib significantly reduced the tumor volume with an inhibition rate of 87.7% as well as tumor weight with an inhibition rate of 73.64% for xenografts in nude mice. The density of microvessel was notably lower in xenografts treated with rofecoxib than in those without treatment (1.5+/-0.2 vs 4.7+/-1.5/200x; P< 0.05). Expression of VEGF protein, MMP-2 progelatinase and MMP-2 mRNA levels in the xenografts treated with rofecoxib were lower than those of control group.


CONCLUSIONS
Antiangiogenesis is one of the mechanisms by which Rofecoxib suppresses pancreatic cancer proliferation.
Zhou
Xu-Chun
XC
Department of Gastroenterology, The First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, 400016, PR China.
Tang
Cheng-Wei
CW
Liu
Chun-Lun
CL
Wang
Chun-Hui
CH
D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy; D013450:Sulfones; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D061965:Matrix Metalloproteinase Inhibitors; D013450:Sulfones; D042461:Vascular Endothelial Growth Factor A; C116926:rofecoxib; D020778:Matrix Metalloproteinase 2