小檗碱抗肿瘤作用与Wnt/-βcaten in信号转导关系

目的证明小檗碱抗肿瘤作用机制可能与信号转导过程的调控有关。方法采用细胞增殖抑制和Hoechst 33258染色凋亡实验比较小檗碱和黄连总碱对人结肠癌HCT116和SW 480细胞的作用。利用Tcf-4报告基因研究小檗碱对肿瘤细胞的信号转导影响。结果小檗碱在5~40 mg.L-1浓度范围内呈浓度依赖性和时间依赖性抑制人结肠癌HCT116和SW 480细胞的增殖;小檗碱(20 mg.L-1)处理72 h后的HCT116和SW 480细胞出现明显凋亡;相当于小檗碱浓度的黄连总碱有类似于小檗碱的作用。20~40 mg.L-1小檗碱和黄连总碱均能明显抑制-βcaten in/Tcf介导的转录活性。结论黄连总碱的抗肿瘤作用可能与其主要成分小檗碱有关;其抗肿瘤作用机制至少与抑制W nt/-βcaten in信号通路有关。

Correlation between antitumor activity of berberine and the inhibition of Wnt/β-catenin signal pathway

Aim To investigate the relationship between the antitumor activity of berberine and the inhibition of Wnt/β-catenin signaling pathway. Methods The antitumor activities of berberine and total alkaloids of Coptis were assessed for their ability to inhibit the proliferation and to induce apopotosis of human colon cancer lines. A well-established Tcf-4 responsive reporter was introduced into human colon cancer lines to test whether berberine and total alkaloids inhibited the β-catenin/Tcf4 activity in these cancer cells.Results The proliferation of HCT116 and SW480 cells was inhibited substantially within the concentration ranges of 5 to 40 mg·L~(1) of berberine. 72 hours after treament both HCT116 and SW480 cells underwent apparent apopotosis as demonstrated by Hoechst 33258 staining. Total alkaloids of Coptis had similar effects to berberine when comparable concentrations of it with berberine were used.Berberine effectively and specifically inhibited the Tcf4 reporter activity, but not the positive control reporter at the same experimental conditions. Conclusion Our findings suggest that berberine may be mainly responsible for the antitumor activity of total alkaloids of Coptis and this effect may be mediated at least in part by its inhibitory effect on the Wnt/β-catenin signaling pathway, which is aberrantly activated in many types of human cancer.