塞来昔布增强氟尿嘧啶对人结肠癌细胞SW480增殖与侵袭的抑制作用  

Celecoxib Enhances the Inhibitory Effect of Fluorouracil on Proliferation and Invasion of SW480 Human Colon Cancer Cells

作　　者：张庆[1] 龙跃平[1] 杜寒松[1] 孙振海[1] 田少博 

机构地区：[1]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022

出　　处：《华中科技大学学报（医学版）》2013年第5期525-529,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2010CDB07701)

摘　　要：目的研究氟尿嘧啶(5Fu)与非甾体类抗炎药(NSAIDs)塞来昔布(Celecoxib)联合对人结肠癌细胞SW480增殖与侵袭的抑制作用。方法运用不同浓度(40、10、1μmol/L)的5Fu单药及联合塞来昔布(50μmol/L)作用于人结肠癌细胞SW480,采用MTT法测定5Fu及其与塞来昔布联合对结肠癌细胞生长的影响,流式细胞仪检测细胞凋亡的变化,Transwell法检测细胞侵袭,Western blot检测Bcl-2、Bax的表达。结果 5Fu与塞来昔布联合可提高对结肠癌细胞的增殖抑制率,与各自单药组及对照组相比较差异均有统计学意义(均P<0.05),且小剂量5Fu(1μmol/L)与塞来昔布联合应用效果更明显(P<0.01),联合用药减弱结肠癌细胞的侵袭力,Western blot检测发现联合用药组比单药组有更显著的Bcl-2表达下降和Bax表达增强。结论塞来昔布与5Fu联合可增强5Fu对结肠癌细胞增殖与侵袭的抑制能力,促进细胞凋亡的作用机制可能与抑制Bcl-2和促进Bax的表达,从而导致细胞内Bcl-2和Bax的比例变化有关。Objective To examine the effect of fluorouracil （5Fu） in combination with celecoxib,a NSAID,on the proliferation and invasion of SW480 human colorectal carcinoma cells. Methods SW480 cells were cultured and treated with 5Fu （40, 10,1 μmol/L） alone or in combination with celeeoxib （50 μmol/L）. MTT assay was used to determine the growth of treated SW480 cells,flow cytometry to detect the cell apoptosis,Transweli assay to measure the invasion of SW480 cells and Western blot to detect the expression of Bcl-2 and Bax in SW480 cells. Results Celecoxib in combination with 5Fu could significantly in- hibit the growth of colorectal carcinoma cells and there was a significant difference in the growth inhibition rate of cells between the combination group and monotherapy group or control group （P〈0.05）. The efficacy was more evident when low dose of 5Fu （1 μmol/L） was used with celecoxib （P〈0.01）. Moreover, the combination administration could weaken the invasion of SW480 cells. Western blot analysis found that the expression of Bcl-2 was significantly decreased and that of Bax significantly increased in the combination group compared with the monotheraphy group. Conclusion Celecoxih in combination with 5Fu can enhance the inhibitory effect of 5Fu on the proliferation and invasion of human colorectal carcinoma cells. It can accelerate the cell apoptosis by inhibiting the expression of Bcl-2, promoting the expression of Bax, and thereby leading to the intraeellular changes of the ratio of Bcl-2/Bax.

关 键 词：塞来昔布 氟尿嘧啶 结肠癌 增殖 侵袭 BCL-2 BAX 

分 类 号：R735.35[医药卫生—肿瘤]