title: Epithelial-mesenchymal transition contributes to docetaxel resistance in human non-small cell lung cancer.
abstract: Lung cancer is an aggressive malignancy with high morbidity and mortality. Chemotherapy has always been the principal treatment measure, but its acquired resistance becomes a critical problem. In the current study, we established a new docetaxel-resistant human non-small lung cancer (NSCLC) cell line A549/Docetaxel. The resistance index (RI) of A549/Docetaxel cells and A549 induced by TGF-β to docetaxel were 8.91 and 11.5, respectively. Compared to the parental A549 cells, the multiplication time of A549/Docetaxel was prolonged, the proportion of the cell cycle in the S phase decreased while that in the G1 phase increased, and apoptotic rate was much lower. The morphology of the resistant cells eventuated epithelial-mesenchymal transition (EMT), which was confirmed by the higher expression of fibronectin, vimentin (mesenchymal markers), and lower expression of E-cadherin (epithelial marker) at mRNA and proteins levels. Furthermore, the representative markers for docetaxel resistance were examined, including ABCB1 (MDR1), Bcl-2, Bax, and tubulin, to figure out the mechanisms of the resistance of A549/Docetaxel. In summary, we have established a typical docetaxel-resistant human NSCLC cell line A549/Docetaxel, and it was suggested that the multidrug resistance of A549/Docetaxel was related to EMT.
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Hailin
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Jiayu
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Lele
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Ningqiang
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Helong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Tangdu Hospital, the Fourth Military Medical UniversityXian, ShaanxiChina.
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D015820:Cadherins; D005353:Fibronectins; D019253:Proto-Oncogene Proteins c-bcl-2; D043823:Taxoids; D016212:Transforming Growth Factor beta; D014404:Tubulin; D014746:Vimentin; D051028:bcl-2-Associated X Protein; D000077143:Docetaxel