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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

阻断IL-6 / GP130信号抑制人胰腺癌细胞中的细胞活力/增殖,糖酵解和集落形成活性

卷 19, 期 5, 2019

页: [417 - 427] 页: 11

弟呕挨: 10.2174/1568009618666180430123939

价格: $65

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摘要

背景:促炎细胞因子白细胞介素-6(IL-6)的产生增加和IL-6信号传导的功能障碍促进肿瘤发生,并且与多种癌症类型中的不良存活结果相关。最近的研究表明,IL-6 / GP130 / STAT3信号通路在胰腺癌的发生和维持中起关键作用。 目的:我们的目标是通过抑制胰腺癌中的IL-6 / GP130信号传导来开发有效的治疗方法。 方法:分别用MTT法和BrdU法测定细胞活力和细胞增殖的影响。通过基于细胞的测定来测定对糖酵解的影响以测量乳酸水平。通过蛋白质印迹和免疫沉淀评估蛋白质表达变化。 siRNA转染用于敲低雌激素受体α基因表达。通过集落形成细胞测定确定集落形成能力。 结果:我们证明IL-6可以诱导胰腺癌细胞活力/增殖和糖酵解。我们还表明,重新利用FDA批准的药物巴西多昔芬可以抑制IL-6 / IL-6R / GP130复合物。 Bazedoxifene还抑制JAK1与IL-6 / IL-6R / GP130复合物的结合和STAT3磷酸化。此外,巴多昔芬阻碍了胰腺癌细胞中IL-6介导的细胞活力/增殖和糖酵解。一致地,其他IL-6 / GP130抑制剂SC144和evista显示出对IL-6刺激的细胞活力,细胞增殖和糖酵解的类似抑制。此外,所有三种IL-6 / GP130抑制剂都降低了胰腺癌细胞中的集落形成能力。 结论:我们的研究结果表明,IL-6刺激胰腺癌细胞增殖,存活和糖酵解,并支持持久性IL-6信号传导是使用IL-6 / GP130抑制剂的胰腺癌的可行治疗靶点。

关键词: IL-6 / GP130信号传导,巴西多昔芬,胰腺癌,细胞活力,细胞增殖,糖酵解,集落形成。

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