title: Inhibition of ZEB1 reverses EMT and chemoresistance in docetaxel-resistant human lung adenocarcinoma cell line.
abstract: Docetaxel has been used as one of the first-line chemotherapies in solid tumors including advanced non-small cell lung cancer (NSCLC). However, limited responses to chemotherapy are observed in clinic and the molecular mechanisms have not been fully understood. Emerging evidence suggests that epithelial-mesenchymal transition (EMT) plays an important role in the processes of tumor metastasis as well as resistance towards anticancer agents. In this study, it was observed that docetaxel-resistant human lung adenocarcinoma cell line (SPC-A1/DTX) was typical of mesenchymal phenotype. SPC-A1/DTX cell line has increased migratory and invasive capacity both in vitro and in vivo. Among the master EMT-inducing transcriptional factors, ZEB1 was found to be significantly increased in SPC-A1/DTX cell line. ZEB1 knockdown with RNA interference could reverse the EMT phenotype and inhibit the migratory ability of SPC-A1/DTX cells. Furthermore, inhibition of ZEB1 significantly enhanced the chemosensitivity of SPC-A1/DTX cells to docetaxel in vitro and in vivo and ectopic expression of ZEB1 increased the chemoresistance of SPC-A1 cells to docetaxel. All these results provide experimental evidence that ZEB1 might be an attractive target for the treatment of human NSCLC.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.forename: Yitian
authors.initials: Y
authors.lastname: Chen
authors.forename: Haizhu
authors.initials: H
authors.lastname: Song
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D048430:Cell Shape; D000077143:Docetaxel; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D043823:Taxoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D043823:Taxoids; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D000077143:Docetaxel