Visfatin mediates doxorubicin resistance in human non-small-cell lung cancer via Akt-mediated up-regulation of ABCC1.

作者: Zhili Cao , Naixin Liang , Huaxia Yang , Shanqing Li

DOI: 10.1111/CPR.12366

关键词: Cancer researchRegulation of gene expressionLung cancerCell cultureDownregulation and upregulationDoxorubicinABCC1ChemistryProtein kinase BGene knockdown

摘要: Objectives Non-small-cell lung cancer (NSCLC) is one of the leading causes deaths worldwide. Increasing levels visfatin are correlated with worse clinical prognosis NSCLC. However, effects on drug resistant still not well illustrated. Materials and methods Effects cells were checked by CCK-8 kit. Gene protein variations measured real-time PCR western blot analysis, respectively. Results Our present data confirmed that expression was significantly increased in NSCLC tissues. In addition, mRNA elevated doxorubicin (Dox) resistance when compared their corresponding sensitivity parental cells. Overexpression can down-regulate Dox up-regulate ABCC1, while has no effect ABCB1. Knockdown ABCC1 Dox-resistant Visfatin increase phosphorylation nuclear localization Akt LY294002 decrease multidrug protein-1 (MRP1) Chromatin immunoprecipitation assays showed overexpression binding promoter both A549 H1793 Conclusions These via activation Akt/MRP1. It indicated inhibition signals might be a promising therapeutic strategy for management chemoresistance patients.

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