Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
Anticancer Res. 2019 Aug;39(8):4031-4041. doi: 10.21873/anticanres.13559.
BACKGROUND/AIM: Eribulin is currently used to treat advanced and metastatic breast cancer in the clinical setting; however, its efficacy is inhibited by resistance acquisition in many cases. Thus, the present study established two eribulin-resistant breast-cancer cell lines, and used these to investigate the mechanisms that underly eribulin-resistance acquisition.
Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin.
The eribulin-resistant cells acquired resistance to eribulin, as well as several other anticancer drugs. After eribulin treatment, the eribulin-resistant cell lines showed no morphological change, no increased expression of epithelial-cadherin, nor any significant alteration in cell-cycle distribution. In contrast, the expression levels of programmed death-ligand 1 were increased in the MCF-7/eribulin-resistant compared to MCF-7 cells.
The herein developed eribulin-resistant cell lines acquired cross-resistance to various anticancer agents, and displayed resistance to eribulin-induced effects on microtubule function and epithelial-mesenchymal transition (EMT).
背景/目的：在临床环境中，埃博霉素目前用于治疗晚期和转移性乳腺癌；然而，在许多情况下，其疗效受到耐药性的抑制。因此，本研究建立了两种埃博霉素耐药的乳腺癌细胞系，并利用这些细胞系来研究获得埃博霉素耐药的机制。
通过用递增浓度的埃博霉素培养 MDA-MB-231 和 MCF-7 细胞，产生埃博霉素耐药的乳腺癌细胞系。
埃博霉素耐药细胞获得了对埃博霉素和其他几种抗癌药物的耐药性。在埃博霉素处理后，埃博霉素耐药细胞系没有形态变化，上皮钙黏蛋白表达没有增加，细胞周期分布也没有明显改变。相比之下，与 MCF-7 细胞相比，MCF-7/埃博霉素耐药细胞系中程序性死亡配体 1 的表达水平增加。
本研究中开发的埃博霉素耐药细胞系获得了对各种抗癌药物的交叉耐药性，并表现出对埃博霉素诱导的微管功能和上皮-间充质转化（EMT）的耐药性。
