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SIRT1通过调节Noxa表达影响非小细胞肺癌细胞株A549对顺铂的敏感性
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SIRT1通过调节Noxa表达影响非小细胞肺癌细胞株A549对顺铂的敏感性
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Journal Article
SIRT1通过调节Noxa表达影响非小细胞肺癌细胞株A549对顺铂的敏感性
2016
Overview
背景与目的非小细胞肺癌的顺铂耐药是常见的临床现象,严重制约了患者的化疗效果,是亟待解决的问题。SIRT1和Noxa的表达变化影响肿瘤细胞对化疗药物的敏感性。本研究旨在研究SIRT1表达对非小细胞肺癌对顺铂的敏感性的影响,并探讨其涉及Noxa表达的机制,以求为提高非小细胞肺癌细胞对顺铂敏感性提供希望。方法利用实时荧光定量PCR和Western blot分析A549细胞及顺铂耐药的A549/DDP细胞SIRT1及Noxa m RNA和蛋白水平的表达差异。利用si RNA干扰技术抑制A549/DDP细胞的SIRT1表达,进而使用Cell Titer Blue试验、流式细胞术从细胞增殖、细胞周期和细胞凋亡方面分析SIRT1沉默对A549/DPP细胞顺铂敏感性的影响。同时利用实时荧光定量PCR和Western blot分析SIRT1抑制对A549/DPP细胞Noxa表达的影响。结果 A549细胞和A549/DDP细胞对顺铂的敏感性有显著差异,与A549细胞相比,A549/DDP细胞的SIRT1表达较高,但Noxa表达较低。使用si RNA抑制A549/DPP细胞的SIRT1表达后,与未抑制SIRT1细胞相比,4μg/m L顺铂处理后的细胞存活率降低,G2期/M期阻滞比例增加,凋亡率提高。同时,SIRT1沉默导致A549/DPP细胞的Noxa表达增加。结论较高的SIRT1可能引起A549细胞对顺铂的耐药性,抑制SIRT1可以提高A549/DDP细胞对顺铂的敏感性,其机制可能涉及SIRT1对Noxa的调节。
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