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鳖甲煎丸对肝癌细胞中Wnt信号通路分子β-连环蛋白和糖原合成酶激酶-3β以及靶基因CD44v6和血管内皮生长因子的影响

[Effect of Biejiajian Pills on Wnt signal pathway molecules β-catenin and GSK-3β and the target genes CD44v6 and VEGF in hepatocellular carcinoma cells].

作者信息

Sun Haitao, He Songqi, Wen Bin, Jia Wenyan, Fan Eryan, Zheng Yan

机构信息

College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.E-mail:

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2014 Oct;34(10):1454-8.

Abstract

OBJECTIVE

To investigate the effect of Biejiajian Pills on the expressions of the signal molecules and target genes of Wnt signal pathway in HepG2 cells and explore the mechanisms by which Biejiajian pills suppress the invasiveness of hepatocellular carcinoma.

METHODS

HepG2 cells were cultured for 48 h in the presence of serum collected from rats fed with Biejiajian Pills. The expressions of β-catenin, GSK-3β and P-GSK-3β in the cultured cells were assessed by Western blotting and the expressions of CD44v6 and VEGF were detected using immunohistochemistry.

RESULTS

HepG2 cells cultured with the serum of rats fed with Biejiajian Pills showed lowered expressions of β-catenin protein both in the cytoplasm and the nuclei with also inhibition of phosphorylation of GSK-3β and reduced expression of CD44v6 and VEGF.

CONCLUSION

Biejiajian Pills can significantly reduce the expression of β-catenin by decreasing the phosphorylation of GSK-3β and blocking the Wnt/β-catenin signaling pathway to cause down-regulation of the target genes CD44v6 and VEGF, which may be one of the molecular mechanisms by which Biejiajian Pills suppress the proliferation and invasiveness of hepatocellular carcinoma.

摘要

目的

探讨鳖甲煎丸对肝癌HepG2细胞中Wnt信号通路信号分子及靶基因表达的影响,探索鳖甲煎丸抑制肝癌侵袭转移的机制。

方法

采用含鳖甲煎丸血清培养HepG2细胞48 h,运用蛋白质免疫印迹法检测细胞中β-连环蛋白(β-catenin)、糖原合成酶激酶-3β(GSK-3β)及磷酸化糖原合成酶激酶-3β(P-GSK-3β)的表达,免疫组化法检测细胞中CD44v6及血管内皮生长因子(VEGF)的表达。

结果

鳖甲煎丸血清培养的HepG2细胞中β-catenin蛋白在胞质及胞核中的表达均降低,同时GSK-3β磷酸化受到抑制,CD44v6及VEGF表达减少。

结论

鳖甲煎丸可能通过降低GSK-3β磷酸化,阻断Wnt/β-catenin信号通路,使靶基因CD44v6及VEGF表达下调,从而显著降低β-catenin的表达,这可能是鳖甲煎丸抑制肝癌细胞增殖及侵袭转移的分子机制之一。

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