title: FoxM1 inhibition enhances chemosensitivity of docetaxel-resistant A549 cells to docetaxel via activation of JNK/mitochondrial pathway.
abstract: Docetaxel is recommended as a second-line chemotherapy agent for the non-small-cell lung cancer (NSCLC); however, drug resistance greatly limits its efficiency. Forkhead box M1 (FoxM1), an oncogenic transcription factor, is believed to be involved in the chemoresistance of various human cancers; whereas the association of FoxM1 with acquired docetaxel-resistance in NSCLC remains unclear. In the present study, we investigated the involvement of FoxM1 in the docetaxel-resistant human lung adenocarcinoma A549 cells (A549/DTX). Our results showed that FoxM1 expression was significantly increased in the A549/DTX cells compared with that in the parental A549 cells. FoxM1 siRNA silencing promoted the cytotoxic and pro-apoptotic effect of docetaxel in A549/DTX cells, which was possibly mediated through inducing the activation of c-Jun N-terminal kinases/mitochondrial signaling pathway. Our results suggest a critical role of FoxM1 in docetaxel-resistance of the A549 cells and form the basis for the development of combined therapy of docetaxel and FoxM1 depletion in treating NSCLC.
authors: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China wangke@jsinm.org.
authors: Ke
authors: K
authors: Wang
authors: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
authors: Xue
authors: X
authors: Zhu
authors: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
authors: Kai
authors: K
authors: Zhang
authors: Save Sight Institute, University of Sydney, NSW 2000, Australia.
authors: Ling
authors: L
authors: Zhu
authors: Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
authors: Fanfan
authors: F
authors: Zhou
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D000072278:Forkhead Box Protein M1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D043823:Taxoids; D000077143:Docetaxel
keywords: FoxM1; chemoresistance; docetaxel; non-small-cell lung cancer