Docetaxel inhibits epithelial-mesenchymal transition in human mammary cells

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 tumour recurrence and resistance, calling for new approaches in cancer treatment. Here we show that prolonged docetaxel treatment at a sub-IC50 concentration inhibits EMT in immortalized human mammary epithelial (HMLE) cells. Using immunofluorescence, flow cytometry, and bulk transcriptomic sequencing to assess EMT progression, we analysed 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. Overall design: Comparative gene expression profiling using RNA-seq data for HMLE cells at 0 and 20 d upon exposure to EMT induction either with or without docetaxel.上皮间质转化（Epithelial–mesenchymal transition, EMT）是一类可逆且动态的生物学过程，在此过程中上皮细胞可获得间质细胞特性，包括增强的干细胞干性与迁移能力。EMT可促进癌症转移，同时也是已知的细胞对多西他赛等常见化疗药物产生耐药性的驱动因素。当前临床采用的多西他赛等化疗方案反而会诱导EMT，增加肿瘤复发与耐药风险，因此亟需开发新型癌症治疗策略。本研究发现，采用亚半数抑制浓度（sub-IC50）的多西他赛进行长期处理，可抑制永生化人乳腺上皮（HMLE）细胞中的EMT进程。研究人员通过免疫荧光（immunofluorescence）、流式细胞术（flow cytometry）及批量转录组测序（bulk transcriptomic sequencing）评估EMT进展，分析了多西他赛处理细胞中一系列EMT相关细胞标志物，观察到在多西他赛存在的情况下，上皮标志物表达上调、间质标志物表达下调。这一结果表明，多西他赛可根据使用浓度兼具双重临床应用价值：不仅可作为细胞毒性化疗药物，还可作为EMT驱动的肿瘤转移与多药耐药抑制剂。总体实验设计：采用RNA-seq数据开展基因表达谱对比分析，研究对象为分别暴露于EMT诱导环境（添加或不添加多西他赛）0天与20天的HMLE细胞。