目的 研究鼠尾草酸（carnosic acid，CA）抑制人结肠癌细胞SW480增殖和增强化疗药物5-氟脲嘧啶（5-Fluorouracil，5-FU）敏感性的作用及机制。方法 结晶紫染色法检测CA对SW480增殖的抑制作用，流式细胞技术分析和MTT法检测CA和5-FU联合使用对人结肠癌细胞SW480凋亡和细胞活力的影响。采用β-catenin荧光素酶报告基因（TOP-Flash）检测CA作用后SW480细胞内β-catenin活性改变。不同浓度CA处理SW480后，Western blot检测β-catenin蛋白质表达水平变化，RT-PCR法检测其下游基因Cyclin D1和P-gp（P-glycoprotein）的mRNA表达水平变化。结果 CA对人结肠癌SW480细胞增殖有抑制作用，且CA能够增强5-FU对结肠癌细胞凋亡和细胞活力的影响。CA处理后细胞内β-catenin转录活性明显降低，Western blot法和RT-PCR法结果显示CA下调了β-catenin的蛋白水平及下游基因Cyclin D1和P-gp mRNA表达。结论 CA能够抑制人结肠癌SW480细胞增殖和增强5-FU的抗肿瘤效果，其机制可能与抑制β-catenin活性并下调其下游基因Cyclin D1和P-gp表达有关。

Objective To investigate the antitumor effects and underlying mechanism of carnosic acid（CA） on the proliferation of human colon cancer SW480 cells and their chemosensitivity to 5-fluorouracil（5-FU）. Methods The anti-proliferation effect of CA on SW480 cells was determined by crystal violet staining. Fluorescence activated cell sorting and MTT assay were utilized to detect the cell apoptosis and cell viability of SW480 cells treated by the combination of CA and 5-FU. The effect of CA on Wnt/β-catenin signaling activity was evaluated by the β-catenin sensitive TOP-Flash luciferase reporter assay. Western blot was applied to detect the expression of β-catenin protein，and RT-PCR was applied to examine Cyclin D1 and P-gp（P-glycoprotein）mRNA expression in SW480 cells after treated with different concentrations of CA. Results CA exhibited the proliferation activity of SW480 colon cancer cells. When used together，CA could enhance the effect of 5-FU on inducing cell apoptosis and reducing cell viability. β-catenin transcription activity and protein level as well as its target genes Cyclin D1 and P-gp mRNA expression were significantly reduced by CA in a concentration-dependent manner. Conclusion CA can inhibit cell proliferation and enhance the antitumor effect of 5-FU on human colon cancer SW480 cells，and its mechanism may be related with the down-regulation of β-catenin activity and its downstream genes expression（Cyclin D1 and P-gp）.

R285.5