罗非昔布对胰腺癌 BXPC-3细胞裸鼠移植瘤血管形成的影响

背景与目的:肿瘤血管形成在肿瘤细胞浸润性生长中起了重要作用,增加表达的环氧合酶-2与快速生长肿瘤中的血管形成有关.本研究目的是观察选择性环氧合酶-2抑制剂-罗非昔布抑制胰腺癌生长的体内效应,以及对胰腺癌移植瘤相关血管形成的影响.方法:将表达有环氧合酶-2的人胰腺癌细胞 BXPC-3种植入裸鼠皮下,形成移植瘤.经口灌入罗非昔布 30 mg· (kg· d)- 1,共 8周,记录肿瘤大小,采用Ⅷ因子免疫组化显示血管密度, BXPC-3细胞上的血管内皮生长因子 (VEGF)检测亦用免疫细胞化学染色.采用 RT-PCR和明胶酶法检测胰腺癌基质金属蛋白酶-2(MMP-2)mRNA的表达及酶活性的变化.结果:罗非昔布对裸鼠胰腺癌移植瘤的肿瘤重量抑瘤率为 73.64%,肿瘤体积抑瘤率为 87.74%.实验组胰腺癌组织微血管密度 [(1.5± 0.2)个 /200倍放大视野 ]明显低于对照组 [(4.7± 1.5)个 /200倍放大视野 ].与对照组比较,罗非昔布显著降低了胰腺癌 BXPC-3细胞中 VEGF、 MMP-2 mRNA的表达以及酶活性.结论:减少胰腺癌相关的血管形成是罗非昔布阻止胰腺癌生长的机制之一.

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.