摘要
目的 研究选择性环氧化酶 2 (COX 2 )抑制剂NS 398的抗结肠癌作用机制及其在 5 氟尿嘧啶 (5 Fu)化疗中的辅助作用。方法 (1)用逆转录 聚合酶链反应 (RT PCR)检测结肠癌HT 2 9、SW4 80细胞COX 2mRNA表达后 ,将NS 398作用于两株细胞 ,用ELISA法测定前列腺素E2(PGE2 )水平。 (2 )将NS 398、5 Fu、NS 398+5 Fu分别作用于两株细胞 ,2 4、4 8和 72h后用MTT法检测细胞增殖状态 ,以流式细胞技术观察药物对细胞凋亡的影响。结果 (1)HT 2 9细胞中COX 2mRNA呈高表达 ,NS 398作用后PGE2表达水平明显降低 ;SW 4 80细胞中COX 2mRNA表达呈阴性 ,NS 398作用后PGE2水平无明显变化。 (2 )NS 398、5 FU呈剂量依赖性方式抑制结肠癌细胞增殖 ,诱导其凋亡 ;NS 398+5 Fu抗增殖的作用较单一用药时更明显 ,而凋亡诱导作用与单一用药差异无显著意义。结论 选择性COX 2抑制剂NS 398具有抗结肠癌作用 ;NS 398抗结肠癌作用可能不依赖于COX 2和PGE2的表达水平 ;NS 398与 5 Fu具有协同的抗增殖作用。
Objective To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitor NS-398 on 5-fluorouracil (5-Fu) chemotherapy and on the progression of colon cells. Methods Colon cancer cells of HT-29 and SW480 lines were cultured. Selective COX-2 inhibitor NS-398, 5-Fu, or NS-398 combining with 5-Fu were added into the cultures to be co-cultured for 24,48, and 72 hours respectively. RT-PCR and ELISA analysis were performed to detect the level of COX-2 mRNA expression and prostaglandin 2 (PGE2) concentration in the cells of both HT-29 and SW480 lines. The proliferation and apoptosis of the two cell lines were observed with MTT assay and flow cytometry. Results Expression of COX-2 mRNA were negative in SW480 line and positive in HT-29 line. Compared with SW480 line, the HT-29 line showed an obvious decline of PGE2 concentration following NS-398 treatment. Both NS-398 and 5-Fu inhibited the cells' proliferation and induced apoptosis in a dose-dependent manner, and a more significant inhibition was found when the cells were co-treated with NS-398 and 5-Fu. Althongh, there was no significant difference between these in inducing apoptosis. Conclusion Selective COX-2 inhibitor NS-398 can inhibit the proliferation of colon cancer cells and induce apoptosis thereof. The mechanism of NS-398 against colon cancer may be independent upon the expression levels of COX-2 mRNA and PGE2 of colon cancer. NS-398 may be a subsidiary drug in 5-Fu chemotherapy in treating colon cancer.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2004年第7期583-586,共4页
National Medical Journal of China
基金
国家自然科学基金资助项目 (3 0 2 712 69)
教育部科学技术研究重点基金资助项目
北京大学"985"科学研究行动计划基金资助项目
