罗非昔布抑制胰腺癌细胞ERK、AP-1信号转导通路

目的研究环氧合酶-2抑制剂-罗非昔布对胰腺癌细胞株BXPC-3增殖的信号转导作用的影响.方法用免疫组化法检测裸小鼠胰腺癌移植瘤中c-Fos的表达,免疫印迹法检测BXPC-3中c-Fos、ERK蛋白的改变,采用EMSA技术检测罗非昔布对胰腺癌细胞AP-1活化的影响.结果罗非昔布可抑制裸小鼠胰腺癌移植瘤c-Fos的表达.随着罗非昔布浓度的增加,胰腺癌细胞中c-Fos、ERK蛋白逐渐下降.EMSA分析显示,20%胎牛血清能刺激胰腺癌细胞BXPC-3中AP-1的活化增加,罗非昔布能抑制这种刺激作用.结论罗非昔布可通过抑制胰腺癌细胞ERK、AP-1信号转导通路,抑制胰腺癌细胞增殖.

The inhibitory effect of rofecoxib on pancreatic cancer via ERK and AP-1

Objective To explore the effect of rofecoxib on the signal transduction pathway in the proliferation of pancreatic cancer cell line BXPC-3. Methods Both protein expression levels of c-Fos and extracellular signal-regulated protein kinase(ERK) was examined in BXPC-3 cells and nude mice with pancreatic carcinoma xenografts by immunohistochemistry and immunoblotting. Activator protein-1 (AP-1) binding activity was detected by electrophoretic mobility shift assay (EMSA). Results The c-Fos and ERK-1/ERK-2 proteins were decreased in the carcinoma tissue of nude mice and BXPC-3 cells both of which treated with rofecoxib by immunohistochemical and immunoblotting analyses. The fetal calf serum(FCS) stimulated AP-1 binding activity on pancreatic cancer cells and rofecoxib could inhibit this response efficiently. Conclusion Rofecoxib, which inhibits not only ERK-1/ ERK-2 and c-Fos expressions but also AP-1 binding activity,results in inhibiting the proliferation of pancreatic cancer cells.