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当代肿瘤药物靶点

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

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Research Article

Fas配体增强RIG-I样受体激动剂和放疗协同作用的肺癌细胞凋亡

卷 20, 期 5, 2020

页: [372 - 381] 页: 10

弟呕挨: 10.2174/1568009620666200115161717

价格: $65

摘要

背景: 视黄酸诱导基因I (RIG-I)样受体(RLRs)在抗病毒反应中发挥关键作用，但最近的研究表明，RLR的激活也能激发抗癌活性，包括细胞凋亡。之前，我们证明了RLR激动剂Poly(I:C)-HMW/LyoVec™[Poly(I:C)-HMW]对人肺癌细胞的抗癌活性可以通过与电离辐射(IR)协同治疗而增强。此外，与Poly(I:C)-HMW和IR共同处理可诱导细胞凋亡，且不依赖于Fas，细胞表面Fas表达增加。 目的: 探讨聚(I:C)-HMW+IR协同作用下Fas配体(FasL)促进肺癌细胞凋亡的假说。 方法: 经Poly(I:C)- HMW+IR共处理24 h后，将FasL加入培养基中，观察细胞表面Fas在人肺癌细胞A549和H1299上的表达。 结果: FasL增强了用聚(I:C)-HMW+IR处理A549细胞和H1299细胞。同样的，单IR -而不是聚(I:C)-HMW-导致细胞表面Fas表达上调，随后对Fas配体诱导的凋亡产生高反应，这表明Poly(I:C) -HMW +IR处理的细胞对fas配体诱导的凋亡的高敏感性是由于细胞对IR的反应。最后，siRNA敲除Fas证实了处理细胞对FasL诱导的凋亡的高应答依赖于Fas的表达。 结论: 综上所述，研究表明，经聚(I:C)-HMW和IR协同治疗后上调的Fas表达对Fas配体诱导的细胞凋亡具有应答作用，而结合RLR激动剂、IR和FasL可能是一种有潜力的肿瘤治疗方法。

关键词: 凋亡，Fas

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