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鳖甲煎丸对肝癌细胞Wnt/β-连环蛋白信号通路及DKK-1和FrpHe基因表达的影响

[Effect of Biejiajian Pills on Wnt/β-catenin signal pathway and DKK-1 and FrpHe gene expressions in hepatocellular carcinoma cells].

作者信息

He Songqi, Cheng Yang, Zhu Yun, Fan Qin, Sun Haitao, Jia Wenyan

机构信息

Southern Medical University, Guangzhou, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2013 Jan;33(1):30-3.

Abstract

OBJECTIVE

To investigate the effect of Biejiajian Pills on Wnt signal pathway and its inhibitory gene (DKK-1 and FrpHe) expressions and explore the mechanism underlying the action of Biejiajian Pills to suppress the invasiveness of hepatocellular carcinoma.

METHODS

Twenty-four Wistar rats were randomized equally into 3 groups for gavage of normal saline and Biejiajian Pills at 20- and 10-fold clinical doses for 3 days. Blood samples were then collected from the rats, and the serum was separated and added in HepG2 cell cultures. After 48 h of culture, the cells were collected to determine the cellular content of β-catenin protein using flow cytometry and detect DKK-1 and FrpHe mRNA expressions using qRT-PCR.

RESULTS

HepG2 cells cultured in the presence of sera from rats fed with Biejiajian Pills showed significantly lowered β-catenin protein expression and obvious down-regulation of DKK-1 mRNA expression, and the effect was correlated with the doses of the drug administered. The expression of FrpHe mRNA showed no significant differences between the 3 groups.

CONCLUSIONS

Biejiajian Pills can effectively inhibit the invasiveness and migration of hepatocellular carcinoma cells, which is closely related to decreased expressions of β-catenin and DKK-1 to cause block of the Wnt/β-catenin signal pathway.

摘要

目的

探讨鳖甲煎丸对Wnt信号通路及其抑制基因(DKK-1和FrpHe)表达的影响,以探究鳖甲煎丸抑制肝癌侵袭的作用机制。

方法

将24只Wistar大鼠随机均分为3组,分别给予生理盐水、20倍临床剂量鳖甲煎丸和10倍临床剂量鳖甲煎丸灌胃3天。然后采集大鼠血液,分离血清并加入HepG2细胞培养体系。培养48小时后,收集细胞,采用流式细胞术检测β-连环蛋白的细胞含量,采用qRT-PCR检测DKK-1和FrpHe mRNA的表达。

结果

用鳖甲煎丸灌胃大鼠的血清培养的HepG2细胞中,β-连环蛋白的表达显著降低,DKK-1 mRNA的表达明显下调,且该作用与给药剂量相关。3组间FrpHe mRNA的表达无显著差异。

结论

鳖甲煎丸可有效抑制肝癌细胞的侵袭和迁移,这与β-连环蛋白和DKK-1表达降低导致Wnt/β-连环蛋白信号通路受阻密切相关。

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