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FNDC5 promotes paclitaxel sensitivity of non-small cell lung cancers via inhibiting MDR1.
Cellular Signalling ( IF 4.4 ) Pub Date : 2020-04-28 , DOI: 10.1016/j.cellsig.2020.109665
Guo-Hua Fan 1 , Tie-Yuan Zhu 1 , Jie Huang 1
Affiliation  

Therapeutic benefits and clinical application of paclitaxel for treating non-small cell lung cancers (NSCLCs) are extremely hampered due to the chemoresistance. A recent study found that fibronectin type III domain-containing protein 5 (FNDC5) was downregulated in NSCLCs cells and negatively correlated with the clinicopathological characteristics in patients with NSCLCs. However, the role and potential molecular basis for FNDC5 in paclitaxel sensitivity of NSCLCs remain unclear. Paclitaxel-sensitive or resistant NSCLCs cell lines were exposed to small interfering RNA against FNDC5 (siFndc5) or recombinant irisin in the presence or absence of paclitaxel. NSCLCs cell lines have decreased FNDC5 expression compared with the normal human lung epithelial cells, which was further downregulated in paclitaxel-resistant cells. Irisin treatment suppressed, whereas Fndc5 silence promoted NSCLCs cells proliferation under basal conditions. Besides, we found that FNDC5 increased paclitaxel chemosensitivity in paclitaxel-sensitive or resistant NSCLCs cell lines via downregulating multidrug resistance protein 1 (MDR1). Further studies revealed that FNDC5 inhibited MDR1 expression via blocking nuclear factor-κB (NF-κB) activation. FNDC5 promotes paclitaxel sensitivity of NSCLCs cells via inhibiting NF-κB/MDR1 signaling, and FNDC5 might be a novel therapeutic target for the treatment of NSCLCs.

中文翻译:

FNDC5 通过抑制 MDR1 促进非小细胞肺癌对紫杉醇的敏感性。

由于化疗耐药性,紫杉醇治疗非小细胞肺癌 (NSCLC) 的治疗效果和临床应用受到极大阻碍。最近的一项研究发现,含纤连蛋白 III 型结构域的蛋白 5(FNDC5)在 NSCLC 细胞中下调,并且与 NSCLC 患者的临床病理特征呈负相关。然而,FNDC5 在 NSCLC 紫杉醇敏感性中的作用和潜在分子基础仍不清楚。在存在或不存在紫杉醇的情况下,将紫杉醇敏感或抗性 NSCLC 细胞系暴露于针对 FNDC5 (siFndc5) 或重组鸢尾素的小干扰 RNA。与正常人肺上皮细胞相比,NSCLC 细胞系 FNDC5 表达降低,在紫杉醇耐药细胞中进一步下调。鸢尾素处理受到抑制,而 Fndc5 沉默在基础条件下促进 NSCLC 细胞增殖。此外,我们发现 FNDC5 通过下调多药耐药蛋白 1 (MDR1) 来增加对紫杉醇敏感或耐药的 NSCLC 细胞系的紫杉醇化学敏感性。进一步的研究表明,FNDC5 通过阻断核因子-κB (NF-κB) 激活来抑制 MDR1 的表达。FNDC5 通过抑制 NF-κB/MDR1 信号通路促进 NSCLC 细胞对紫杉醇的敏感性,FNDC5 可能成为治疗 NSCLC 的新治疗靶点。进一步的研究表明,FNDC5 通过阻断核因子-κB (NF-κB) 激活来抑制 MDR1 的表达。FNDC5 通过抑制 NF-κB/MDR1 信号通路促进 NSCLC 细胞对紫杉醇的敏感性,FNDC5 可能成为治疗 NSCLC 的新治疗靶点。进一步的研究表明,FNDC5 通过阻断核因子-κB (NF-κB) 的激活来抑制 MDR1 的表达。FNDC5 通过抑制 NF-κB/MDR1 信号通路促进 NSCLC 细胞对紫杉醇的敏感性,FNDC5 可能成为治疗 NSCLC 的新治疗靶点。
更新日期:2020-04-28
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