Wataru Goto1, Shinichiro Kashiwagi2, Yuka Asano1, Koji Takada1, Katsuyuki Takahashi3, Hisakazu Fujita4, Tsutomu Takashima1, Masatsune Shibutani5, Ryosuke Amano6, Shuhei Tomita3, Kosei Hirakawa1,5, Masaichi Ohira1,5. 1. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 2. Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan spqv9ke9@view.ocn.ne.jp. 3. Department of Pharmacology, Osaka City University Graduate School of Medicine, Osaka, Japan. 4. Department of Scientific and Linguistic Fundamentals of Nursing, Osaka City University Graduate School of Nursing, Osaka, Japan. 5. Department of Gastrointestinal Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan. 6. Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Abstract
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. MATERIALS AND METHODS: Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin. RESULTS: 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. CONCLUSION: 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). Copyright
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. MATERIALS AND METHODS:Eribulin-resistant breast-cancer cell lines were generated by culturing MDA-MB-231 and MCF-7 cells with increasing concentrations of eribulin. RESULTS: 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. CONCLUSION: 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). Copyright