塞来昔布联合PDTC对人结肠癌细胞HT-29的抑制增殖和促凋亡作用及其机制  

Anti- proliferative and pro-apoptotic effects of celecoxib combined with PDTC on human colon cancer cell HT-29 in vitro

作　　者：王永翔[1] 师水生[1] 王洋[1] 马西强 谢江柳 刘庆彤[1] 陈永华[1] 

机构地区：[1]山西医科大学第二医院消化内科,太原市030001

出　　处：《中国临床研究》2014年第7期769-772,共4页Chinese Journal of Clinical Research

摘　　要：目的研究塞来昔布联合吡咯烷二硫氨基甲酸(PDTC)对人结肠癌细胞HT-29增殖、凋亡的影响及其对COX-2、NF-κB、Caspase-3基因表达的影响,探讨塞来昔布联合用药抗肿瘤的机制。方法用不同浓度的塞来昔布(30、60、120、240μmol/L)(单药组)以及不同浓度塞来昔布联合不同浓度的PDTC(50、100μmol/L)(联合组)分别处理人结肠癌细胞,采用CCK-8法检测细胞的增殖情况,流式细胞术分析细胞凋亡情况,实时荧光定量PCR检测各组细胞COX-2、NF-κB、Caspase-3表达的变化。结果塞来昔布单药组对结肠癌细胞具有抑制增殖、促进凋亡作用,其作用随着药物浓度、给药时间的增加而增强(P均<0.05);同时检测到COX-2、NF-κB mRNA的表达降低(P均<0.05),Caspase-3表达升高(P<0.05),且具有浓度依赖性;联合组较同一塞来昔布浓度的单药组上述作用更明显(P均<0.05)。结论塞来昔布单药组和联合组均能抑制人结肠癌细胞的增殖,促进其凋亡;联合组作用强于单药组;其机制可能与COX-2、NF-κB的下调和Caspase-3表达上调有关。Objective To research the influences of celecoxib combined with pyrrolidine dithiocarbamate （PDTC） on proliferation and apoptosis of colon cancer cell HT-29 and on gene expressions of COX-2, NF-kappaB, Caspase-3 and explore its potential mechanism of anti-tumor effect. Methods The human colon cancer cells were dealt by different concentrations of celecoxib alone （ single-drug group） or celecoxib combined with different concen- trations of PDTC （combination group）. The proliferation of the cells was assayed by CCK-8 method; the apoptosis of the cells was assessed by the flow cytometry; the expressions of COX-2, NF-kappaB and Caspase-3 were detected by quantitative real time polymerase chain reaction （PCR）. Results In single-drug group, the proliferation of human colon cancer cells was inhibited, and the cell apoptosis was promoted all with dose- and time-dependent manner （ all P 〈 O. 05 ） ; the expressions of COX-2 and NF-kappaB mRNA were down-regulated, and the expression of Caspase-3 was up-regulated all with concentration-dependent manner （all P 〈 0.05 ）. The aforementioned effects in combina- tion group were more obvious than those in corresponding single-drug group （ all P 〈 0.05 ）. Conclusions In two groups, the proliferation of HT-29 cells is inhibited, and the apoptosis of HT-29 cells is promoted, while the effects in combination group are all superior to those in single-drug group. The mechanism may be related to down-regulation of COX-2 and NF-kappaB expressions and up-regulation of Caspase-3 expression.

关 键 词：塞来昔布 吡咯烷二硫氨基甲酸 结肠癌 增殖 细胞凋亡 

分 类 号：R735.35[医药卫生—肿瘤]