Zhili Cao1, Naixin Liang1, Huaxia Yang2, Shanqing Li1. 1. Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China. 2. Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Abstract
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 ABCC1, while has no effect on ABCB1. Knockdown of visfatin can down-regulate the expression of ABCC1 in Dox-resistant NSCLC cells. Visfatin can increase the phosphorylation and nuclear localization of Akt in NSCLC cells. LY294002 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 ABCC1 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.
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 ABCC1, while has no effect on ABCB1. Knockdown of visfatin can down-regulate the expression of ABCC1 in Dox-resistant NSCLC cells. Visfatin can increase the phosphorylation and nuclear localization of Akt in NSCLC cells. LY294002 can decrease the expression of multidrug resistance protein-1 (MRP1) in NSCLCDox-resistant cells. Chromatin immunoprecipitation assays showed that overexpression of visfatin can significantly increase the binding of Akt with the promoter of ABCC1 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 NSCLCpatients.
Authors: Laurie E Gaspar; Kari Chansky; Kathy S Albain; Eric Vallieres; Valerie Rusch; John J Crowley; Robert B Livingston; David R Gandara Journal: J Clin Oncol Date: 2005-05-01 Impact factor: 44.544
Authors: S P Cole; G Bhardwaj; J H Gerlach; J E Mackie; C E Grant; K C Almquist; A J Stewart; E U Kurz; A M Duncan; R G Deeley Journal: Science Date: 1992-12-04 Impact factor: 47.728