Open AccessVisfatin mediates doxorubicin resistance in human non–small‐cell lung cancer via Akt‐mediated up‐regulation of ABCC 1
Author(s) -
Cao Zhili,
Liang Naixin,
Yang Huaxia,
Li Shanqing
Publication year - 2017
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12366
Subject(s) - gene knockdown , protein kinase b , cancer research , chromatin immunoprecipitation , western blot , doxorubicin , lung cancer , cancer cell , downregulation and upregulation , pi3k/akt/mtor pathway , cancer , phosphorylation , biology , medicine , cell culture , signal transduction , gene expression , gene , microbiology and biotechnology , promoter , biochemistry , chemotherapy , genetics
Objectives Non–small‐cell lung cancer ( NSCLC ) is one of the leading causes of cancer deaths worldwide. Increasing levels of visfatin are correlated with worse clinical prognosis of NSCLC . However, the effects of visfatin on drug resistant are still not well illustrated. Materials and methods Effects of visfatin on drug resistant cells were checked by CCK ‐8 kit. Gene and protein variations were measured by real‐time PCR and western blot analysis, respectively. Results Our present data confirmed that expression of visfatin was significantly increased in NSCLC cells and tissues. In addition, protein and mRNA expression of visfatin were significantly elevated in doxorubicin (Dox) resistance of NSCLC cells when compared with their corresponding sensitivity parental cells. Overexpression of visfatin can down‐regulate the Dox sensitivity of NSCLC cells and up‐regulate the mRNA and protein expression of ABCC 1, while has no effect on ABCB 1. Knockdown of visfatin can down‐regulate the expression of ABCC 1 in Dox‐resistant NSCLC cells. Visfatin can increase the phosphorylation and nuclear localization of Akt in NSCLC cells. LY 294002 can decrease the expression of multidrug resistance protein‐1 (MRP1) in NSCLC Dox‐resistant cells. Chromatin immunoprecipitation assays showed that overexpression of visfatin can significantly increase the binding of Akt with the promoter of ABCC 1 in both A549 and H1793 cells. Conclusions These data showed that visfatin can decrease Dox sensitivity of NSCLC cells via activation of Akt/MRP1. It indicated that inhibition of visfatin signals might be a promising therapeutic strategy for the management of chemoresistance of NSCLC patients.