芹菜素增强阿司匹林对结肠癌细胞的增殖抑制作用及其机制研究

Apigenin enhances the proliferative inhibition effect of aspirin in colon cancer cells by inhibiting COX-2

  • 摘要:
      目的  研究芹菜素(apigenin)能否增强阿司匹林(aspirin)对结肠癌细胞系的增殖抑制作用, 并阐述其机制。
      方法  选取HT-29、HCA-7、Moser和DLD-1细胞系, 设置空白对照组、芹菜素(10μmol/L)组、阿司匹林(2.5、5、10 mmol/L)组、联合用药组。MTT法检测细胞存活率。免疫印迹法和逆转录多聚酶链式反应(RT-PCR)检测不同处理方式对Moser细胞环氧合酶-2(cy clooxygenase-2, COX-2)表达的影响。免疫印迹法检测不同处理方式对由TNF-α诱导的IκBα降解的抑制, 以此来反映不同处理方式对NF-κB活性的影响。
      结果  芹菜素呈剂量和时间依赖性地增强阿司匹林对表达COX-2的结肠癌细胞增殖的抑制, 并协同增强阿司匹林对COX-2表达的抑制和对TNF-α诱导的IκBα降解的抑制。
      结论  芹菜素能通过抑制COX-2的表达而增强阿司匹林对结肠癌细胞的增殖抑制。

     

    Abstract:
      Objective  This study aimed to determine whether apigenin can enhance the inhibitory effect of aspirin on colorectal cancer cell lines and to investigate the underlying mechanism in vitro.
      Methods  The colorectal cancer cell lines HT-29, HCA-7, Moser, and DLD-1 were selected for this study.All cell lines were divided into four groups: control group, group treated with 10 μmol/L apigenin, group treated with aspirin at 2.5, 5, and 10 mmol/L, and group treated with apigenin and aspirin at varying concentrations.Apigenin was applied 2 h prior to aspirin addition.Cell viability was detected by MTT assay at 24, 48, and 72 h post-treatment.Western blot and reverse-transcription polymerase chain reaction analysis were performed to determine the effect of different treatments on the expression of COX-2 in Moser cells 48 h after treatment.Protection of IκBα degradation by TNF-α treatment was detected by Western blot analysis to validate the effect of apigenin and aspirin against NF-κB activation.
      Results  Apigenin enhanced the inhibitory effect of aspirin on colorectal cancer cells in a dose-and time-dependent manner.The effect was correlated with the suppression of COX-2 expression.COX-2 expression was markedly inhibited in the combined treatment group.In addition, combined treatment resulted in a remarkable inhibition of the TNF-α-induced degradation of IκBα.
      Conclusion  Apigenin can potentiate the inhibitory effect of aspirin on colorectal cancer cells by inhibiting COX-2 expression.

     

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