Docetaxel Inhibits Epithelial-Mesenchymal Transition in Human Mammary Cells.

Autor: Beerkens SJ; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia., King JJ; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia., Irving KL; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia., Bhatia S; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.; School of Biological/Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4000, Australia.; Translational Research Institute, Brisbane, Queensland 4102, Australia., Thompson EW; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.; School of Biological/Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4000, Australia.; Translational Research Institute, Brisbane, Queensland 4102, Australia.; Invasion and Metastasis Unit, St Vincent's Institute, Melbourne, Victoria 3065, Australia., Smith NM; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia., Iyer KS; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia., Evans CW; School of Molecular Sciences, The University of Western Australia, 35 Stirling Highway, Perth, Western Australia 6009, Australia.
Jazyk: angličtina
Zdroj: Molecular pharmaceutics [Mol Pharm] 2024 Jan 01; Vol. 21 (1), pp. 53-61. Date of Electronic Publication: 2023 Nov 29.
DOI: 10.1021/acs.molpharmaceut.3c00425
Abstrakt: Epithelial-mesenchymal transition (EMT) is a reversible and dynamic biological process in which epithelial cells acquire mesenchymal characteristics including enhanced stemness and migratory ability. EMT can facilitate cancer metastasis and is a known driver of cellular resistance to common chemotherapeutic drugs, such as docetaxel. Current chemotherapeutic practices such as docetaxel treatment can promote EMT and increase the chance of tumor recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC 50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analyzed a range of cellular markers of EMT in docetaxel-treated cells and observed an upregulation of epithelial markers and downregulation of mesenchymal markers in the presence of docetaxel. This finding suggests that docetaxel may have clinical applications not only as a cytotoxic drug but also as an inhibitor of EMT-driven metastasis and multidrug resistance depending on the concentration of its use.
Databáze: MEDLINE