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: Weiwei Shen, Hailin Pang, Jiayu Liu, Jing Zhou, Feng Zhang, Lele Liu, Ningqiang Ma, Ning Zhang, Helong Zhang, Lili Liu
• Journal: Oncology research (Oncol Res) Vol. 22 Issue 1 Pg. 47-55 ( 2014) ISSN: 1555-3906 [Electronic] United States
• PMID: 25700358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Biomarkers, Tumor
• Cadherins
• Fibronectins
• Proto-Oncogene Proteins c-bcl-2
• Taxoids
• Transforming Growth Factor beta
• Tubulin
• Vimentin
• bcl-2-Associated X Protein
• Docetaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Apoptosis
• Biomarkers, Tumor (metabolism)
• Cadherins (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Cycle
• Cell Growth Processes
• Cell Line, Tumor
• Docetaxel
• Drug Resistance, Neoplasm (physiology)
• Epithelial-Mesenchymal Transition
• Fibronectins (metabolism)
• Humans
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Taxoids (pharmacology)
• Transforming Growth Factor beta (metabolism)
• Tubulin (metabolism)
• Vimentin (metabolism)
• bcl-2-Associated X Protein (metabolism)