[Effects of rofecoxib on angiogenesis of pancreatic cancer xenograft in nude mice].

Background & 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.

Conclusion: Antiangiogenesis is one of the mechanisms by which Rofecoxib suppresses pancreatic cancer proliferation.