丙谷胺、阿司匹林对人结肠癌HT-29细胞增殖的抑制作用  

Synergistic actions of proglumide and aspirin against human colon cancer HT- 29 cells

作　　者：朱蓉[1] 赵逵[1] 方兴国[1] 付晓菲[1] 狄连君[1] 陈小燕[1] 李优锋[1] 

机构地区：[1]遵义医学院附属医院消化内科,贵州遵义563099

出　　处：《遵义医学院学报》2013年第6期536-541,共6页Journal of Zunyi Medical University

基　　金：贵州省高层次人才科研条件特助经费项目(NO:TZJF-2011-32)

摘　　要：目的探讨丙谷胺和阿司匹林对人结肠癌细胞株HT-29增殖的协同抑制作用及可能的机制。方法采用噻唑蓝(MTT)比色法检测胃泌素受体拮抗剂丙谷胺和非甾体类抗炎药阿司匹林分别及联合应用对HT-29细胞增殖的影响;采用实时定量逆转录聚合酶链反应(Real-time PCR)和蛋白印迹法(Western blot)检测丙谷胺和阿司匹林分别干预以及联合用药48h后COX-2和15-PGDH mRNA和蛋白质的表达情况。结果丙谷胺和阿司匹林分别呈时间和剂量依赖性地抑制HT-29细胞的增殖,且二者具有协同作用;丙谷胺单一用药时,COX-2mRNA和蛋白质表达下调,15-PGDH mRNA和蛋白质表达上调(P<0.05);阿司匹林单一用药时,COX-2、15-PGDH mRNA和蛋白质的表达均无明显变化;两药联合应用时,COX-2 mRNA和蛋白质的表达显著下调,15-PGDH mRNA和蛋白质的表达显著上调,与对照组以及各单一用药组比较差异均具有统计学意义(P<0.05)。结论丙谷胺、阿司匹林联合应用协同抑制HT-29细胞增殖,此作用可能通过下调COX-2表达,上调15-PGDH表达这一机制来实现。Objective To investigate proglumide and aspirin co -inhibiting effect on proliferation of cultured human colon cancer HT-29 cells. Methods Applying proglumide （the gastrin receptor antago- nist） and aspirin （non-steroidal anti -inflammatory drugs） on cultured human colon cancer cell line HT-29 separately and jointly, using the MTT colorimetrie assay to detect proliferation rates of HT-29 cells. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect COX-2 and 15-PGDH mRNA expression levels, Western blotting to detect COX-2 and 15-PGDH protein expression levels. Results Proglumide and aspirin, inhibited the proliferation of HT - 29 cells, respectively in a time - and dose - dependent manner. The ICs0 of proglumide was 20. 248 retool/L, the ICs0 of aspirin was 4. 996 mmol/L. The Combination of two agents had a synergistic in- hibitory effect. Proglumide reduced the COX-2 mRNA and protein＇s expressions and increased the 15 - PGDH mRNA and protein ＇ s expressions in HT - 29 cells , compared with the control group （P 〈 0. 05 ）. Aspirin reduced the COX - 2 mRNA and protein＇ s expressions and increased the 15 - PGDH mR-NA and protein＇ s expression of HT - 29 cells, to some extents, but there was no statistical significance. Proglumide combined with aspirin reduce the COX -2 mRNA and protein＇ s expressions and increased the 15 - PGDH mRNA and protein＇ s expressions of HT - 29 cells significantly, compared with the con-trol group, the proglumide group and the aspirin group （ P 〈 0.05 ）. Conclusion Proglumide and asprin inhibit the proliferation of cultured colon cancer HT - 29 cells synergistiely, probably though inhibiting the expressions of COX -2 and promoting the expressions of 15 -PGDH.

关 键 词：丙谷胺 阿司匹林 环氧合酶-2 15-羟基前列腺素脱氢酶 结肠癌细胞株 

分 类 号：R574.62[医药卫生—消化系统]