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New basic approach to treat non‐small cell lung cancer based on RNA‐interference

机译:基于RNA干扰的治疗非小细胞肺癌的新基本方法

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AbstractBackgroundTo date the therapy for non-small cell lung cancer (NSCLC) is associated with severe side effects, frustrating outcomes, and does not consider different tumor characteristics. The RNA-interference (RNAi) pathway represents a potential new approach to treat NSCLC. With small interfering ribonucleic acids (siRNAs), it is possible to reduce the expression of proliferation-dependent proteins in tumor cells, leading to their apoptosis. We propose that siRNAs could be adapted to the tumor type and may cause fewer side effects than current therapy.MethodsFour NSCLC cell lines were cultured under standard conditions and transfected with three different concentrations of siRNAs targeted against the hypoxia-inducible factors 1α and 2α (HIF1α and HIF2α) and signal transducer and activator of transcription 3 (STAT3). The expression was observed by quantitative real-time polymerase chain reaction and western blots. For the analysis of cell growth three days after transfection, the cell number was detected using a CASY cell counter system.ResultsThe results of the silencing of the analyzed factors differ in each cell line. Cell growth was significantly reduced in all cell lines after transfection with HIF1α- and STAT3-siRNA. The silencing of HIF2α resulted in a significant effect on cell growth in squamous, and large-cell lung cancer.ConclusionsThis study shows that the knockdown and viability to siRNA transfection differ in each tumor type according to the used siRNA. This implies that the tumor types differ among themselves and should be treated differently. Therefore, the authors suggest a possible approach to a more personalized treatment of NSCLC.
机译:摘要背景迄今为止,非小细胞肺癌(NSCLC)的治疗与严重的副作用,令人沮丧的结果有关,并且没有考虑不同的肿瘤特征。 RNA干扰(RNAi)途径代表了一种治疗NSCLC的潜在新方法。使用小的干扰核糖核酸(siRNA),可以减少肿瘤细胞中增殖依赖性蛋白的表达,从而导致其凋亡。我们建议siRNA可以适应肿瘤类型,并且可能比目前的治疗产生更少的副作用。方法在标准条件下培养4种NSCLC细胞系,并用针对低氧诱导因子1α和2α(HIF1α)的三种不同浓度的siRNA转染。和HIF2α)以及信号转导和转录激活因子3(STAT3)。通过定量实时聚合酶链反应和蛋白质印迹观察表达。对于转染三天后的细胞生长分析,使用CASY细胞计数器系统检测细胞数。结果在每种细胞系中,分析因子的沉默结果不同。用HIF1α-和STAT3-siRNA转染后,所有细胞系的细胞生长均显着降低。 HIF2α的沉默对鳞状和大细胞肺癌细胞的生长产生了显着影响。这意味着肿瘤类型之间存在差异,应区别对待。因此,作者提出了一种可能的方法,以更个性化的方式治疗NSCLC。

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