Celecoxib Downregulates CD133 Expression Through Inhibition of the Wnt Signaling Pathway in Colon Cancer Cells
Celecoxib Downregulates CD133 Expression Through Inhibition of the Wnt Signaling Pathway in Colon Cancer Cells
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塞来昔布通过抑制结肠癌细胞中的 Wnt 信号通路下调 CD133 表达
DOI：
10.3109/07357907.2012.754458
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发表时间：
2013-02-01
影响因子：
2.4
通讯作者：
Lin, Edward H.
中科院分区：
文献类型：
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作者：
Deng, Yanhong;Su, Qiao;Lin, Edward H.
结肠癌中的CD 133阳性癌症干细胞对常规化疗具有抗性。本研究的目的是研究考克斯-2抑制剂塞来昔布对HT 29和DLD 1细胞中CD 133表达的影响。用不同浓度和持续时间的塞来昔布处理HT 29和DLD 1细胞。流式细胞术、免疫印迹、免疫荧光和实时定量PCR检测CD 133表达。通过荧光素酶测定来测量Wnt信号通路活性，并且使用微阵列分析来监测基因表达变化。随着塞来昔布浓度的增加或暴露时间的延长，HT 29细胞的CD 133表达水平显著降低。HT 29和DLD 1细胞中CD 133 mRNA的相对表达也随着药物暴露而降低。此外，HT 29和DLD 1细胞中的Wnt活化随着塞来昔布处理而降低。基因表达谱芯片显示，Lgr 5、Oct 4、Prominin-1、Prominin-2、CXCR 4、E2 F8、CDK-2等干性基因下调，CEACAM 5、GDF、ADFP、ICAM 1等分化基因上调。我们的研究结果表明，CD 133表达下调塞来昔布通过抑制Wnt信号通路，这可能是导致细胞分化。
CD133-positive cancer stem cells in colon cancer are resistant to conventional chemotherapy. The aim of the present study was to investigate the effect of celecoxib, a COX-2 inhibitor, on CD133 expression in HT29 and DLD1 cells. HT29 and DLD1 cells were treated with celecoxib using different concentrations and duration. CD133 expression was detected by flow cytometry, Western blotting, immunofluorescence, and quantitative real-time PCR. Wnt signaling pathway activity was measured by luciferase assay and gene expression changes were monitored using microarray analysis. HT29 cells showed significantly decreasing levels of CD133 expression with increasing concentrations of or duration of exposure to celecoxib. CD133 mRNA relative expression in HT29 and DLD1 cells also decreased with drug exposure. Furthermore, Wnt activation in HT29 and DLD1 cells decreased with celecoxib treatment. Gene expression microarray showed stemness genes, including Lgr5, Oct4, Prominin-1, Prominin-2, CXCR4, E2F8, CDK-2, were downregulated and differentiation genes, including CEACAM5, GDF, ADFP, ICAM1, were upregulated. Our results show that CD133 expression was downregulated by celecoxib through inhibition of the Wnt signaling pathway, which may be lead to cell differentiation.