摘要
目的探讨非甾体类抗炎药Celecoxib对人卵巢癌环氧合酶2(COX-2)表达的影响,以及其抗卵巢癌作用与COX-2表达之间的关系。方法采用流式细胞技术(FCM)、逆转录-聚合酶链反应(RT-PCR)和Western免疫印迹法,检测不同浓度Celecoxib(COX-2特异性抑制剂)加入人卵巢癌SKOV3细胞株中共同培养24h后,SKOV3细胞COX-2的蛋白表达和mRNA水平变化,同时与非选择性COX-2抑制剂Aspirin相比较。采用免疫组化法检测Celecoxib对人卵巢癌裸鼠移植瘤组织中COX-2表达的影响。结果RT-PCR显示,随药物浓度增加,COX-2mRNA表达逐渐下降,与对照组比较,差异有统计学意义(P<0.05);FCM显示,Celecoxib(5×10-5mol/L)和Aspirin(7×10-3mol/L)组COX-2的平均荧光强度明显低于对照组(P<0.05),尤以Celecoxib(5×10-5mol/L)组更显著;Westernblot检查结果相同;免疫组化发现,Celecoxib不同剂量(10、25、50mg/kg·d)用于人卵巢癌裸鼠移植瘤后,其COX-2的IOD值均明显低于对照组(P<0.05),且随药物剂量的增大,其IOD减小。结论Celecoxib对人卵巢癌的抗肿瘤效应与COX-2表达下降有关,可能存在COX-2依赖和非依赖途径,值得进一步研究。
Objective To explore the effects of nonsteroidal anti-inflammatory drug Celecoxib on the expression of cyclooxygenase-2 (COX-2) in the SKOV3 cell line and the xenografted nude mice of ovarian carcinoma. Methods The expression of COX-2 in the SKOV3 cell was determined by reverse transcription polymerase chain reaction (RT-PCR), flow cytometry (FCM), and Western blot analysis. The expression of COX-2 in tumor cells was measured with Immunocytochemistry. Results RT-PCR showed that the expression COX-2 mRNA was strongly down-regulated in SKOV3 cells after treatment with Celecoxib or Aspirin. FCM and Western blot analysis showed that the protein product of COX-2 was strongly decreased by Celecoxib or Aspirin. The Celeeoxib was more potential effects than Aspirin. The immunocytochemistry result showed that the expression of COX-2 in 10, 25, 50 mg/kg · d of Celecoxib were lower obviously than it in the control group in Xenografted nude mice. Conclusion The anticarcinogenic effects of Celecoxib is probably related to the down- regulation of COX-2, and can be explained to both COX-2-dependent and -independent mechanisms.
出处
《四川大学学报(医学版)》
CAS
CSCD
北大核心
2006年第5期757-760,共4页
Journal of Sichuan University(Medical Sciences)