The Cancer Stem Cell Inhibitor Napabucasin (BBI608) Shows General Cytotoxicity in Biliary Tract Cancer Cells and Reduces Cancer Stem Cell Characteristics
The Cancer Stem Cell Inhibitor Napabucasin (BBI608) Shows General Cytotoxicity in Biliary Tract Cancer Cells and Reduces Cancer Stem Cell Characteristics
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肿瘤干细胞抑制剂Napabucasin （BBI608）在胆道癌细胞中显示出一般的细胞毒性，并降低肿瘤干细胞的特征
DOI：
10.3390/cancers11030276
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发表时间：
2019-03-01
期刊：
影响因子：
5.2
通讯作者：
Mayr, Christian
中科院分区：
文献类型：
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作者：
Beyreis, Marlena;Gaisberger, Martin;Mayr, Christian
胆道癌是一种具有有限治疗选择的毁灭性疾病。胆道癌中可能存在肿瘤干细胞。Napabucasin是一种先前描述的癌症干细胞抑制剂，目前正在临床试验中使用。然而，尚未获得关于napabucasin和胆道癌的数据。我们使用刃天青测定和膜联蛋白V/7-AAD染色测试了纳帕布卡辛对综合性胆道癌体外模型的一般细胞毒性作用。通过软琼脂测定、脱氢酶-1测定、表面CD 326表达的测量和克隆形成生长的测量来分析napabucasin对功能性癌症干细胞特征的影响。使用Western印迹和基于逆转录-PCR的人癌症干细胞阵列进行纳帕布卡辛对癌症干细胞蛋白和基因表达的影响的评估。Napabucasin显示出浓度和细胞系依赖性的细胞毒性作用，并增加凋亡和坏死细胞分数。用napabucasin治疗显著减少了肿瘤球的形成和克隆形成生长，以及CD 326表面表达。在蛋白质和mRNA水平上，napabucasin治疗后癌症干细胞标志物的表达降低。我们的研究提供了关于napabucasin作为治疗胆道癌的有前途的物质的第一个数据。
Biliary tract cancer is a devastating disease with limited therapeutic options. The involvement of cancer stem cells in biliary tract cancer is likely. Napabucasin is a previously described cancer stem cell inhibitor that is currently being used in clinical trials. However, data regarding napabucasin and biliary tract cancer are not available yet. We tested the general cytotoxic effect of napabucasin on a comprehensive biliary tract cancer in vitro model, using resazurin assay and Annexin V/7-AAD staining. The effect of napabucasin on functional cancer stem cell characteristics was analyzed via soft agar assay, aldehyde-dehydrogenase-1 assay, measurement of surface CD326 expression, and measurement of clonogenic growth. The evaluation of the effect of napabucasin on cancer stem cell protein and gene expression was performed using Western blot and reverse transcription-PCR-based human cancer stem cell array. Napabucasin showed a concentration-and cell line-dependent cytotoxic effect, and increased the apoptotic and necrotic cell fractions. Treatment with napabucasin significantly reduced the formation of tumor spheres and clonogenic growth, as well as CD326 surface expression. Expression of cancer stem cell markers were reduced following napabucasin treatment on the protein and mRNA levels. Our study provides first data regarding napabucasin as a promising substance for the treatment of biliary tract cancer.