β-连环蛋白抑制剂与索拉非尼在肝癌细胞中的协同作用。
Synergistic effects of β-catenin inhibitors and sorafenib in hepatoma cells.
机构信息
Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany.
Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany
出版信息
Anticancer Res. 2014 Sep;34(9):4677-83.
BACKGROUND/AIM: The kinase inhibitor sorafenib is the only approved drug which is effective against late-stage hepatocellular carcinoma (HCC). However, the mean survival of patients is still less than one year, making new approaches for tumor treatment essential. Oncogenic signaling through β-catenin is frequently overactivated in HCC and therefore a potential target for a combination therapy with sorafenib.
MATERIALS AND METHODS
Two hepatoma cell lines were treated with non-cytotoxic concentrations of sorafenib and different β-catenin inhibitors. The tumor-relevant end-points of proliferation, apoptosis, cell migration, and colony formation were assessed in vitro along with the activity of the Wingless/Int-1(WNT)/β-catenin and mitogen-activated protein kinase pathways.
RESULTS
Combined treatment with sorafenib and β-catenin inhibitors synergized in the inhibition of cell proliferation, migration, colony formation ability, and induction of apoptosis.
CONCLUSION
In vitro data suggest that the combination of sorafenib and β-catenin inhibition might be a promising approach for HCC treatment.
背景/目的：激酶抑制剂索拉非尼是唯一一种对晚期肝细胞癌（HCC）有效的批准药物。然而，患者的平均存活时间仍不到一年，因此有必要探索新的肿瘤治疗方法。β-连环蛋白的致癌信号在 HCC 中经常过度激活，因此它是与索拉非尼联合治疗的潜在靶点。
材料和方法
用非细胞毒性浓度的索拉非尼和不同的β-连环蛋白抑制剂处理两种肝癌细胞系。在体外评估与 Wnt/β-连环蛋白和丝裂原激活蛋白激酶通路活性相关的增殖、凋亡、细胞迁移和集落形成等肿瘤相关终点。
结果
索拉非尼和β-连环蛋白抑制剂联合治疗可协同抑制细胞增殖、迁移、集落形成能力和诱导凋亡。
结论
体外数据表明，索拉非尼和β-连环蛋白抑制的联合治疗可能是 HCC 治疗的一种有前途的方法。
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