Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma.
Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma.
复制标题
甲磺酸艾日布林对软组织肉瘤的抗有丝分裂和非有丝分裂作用。
作者：
S. Kawano;M. Asano;Y. Adachi;J. Matsui
背景
甲磺酸艾日布林（eribulin mesilate，eribulin）是一种基于软海绵素B的微管动力学抑制剂，除了在乳腺癌模型中具有抗有丝分裂活性外，还能促进血管重塑和上皮-间质转化（EMT）逆转。
材料和方法
在几种人软组织肉瘤（STS）细胞系中检测了艾日布林的体外和体内抗增殖活性。为了评估肿瘤血液灌注和表型变化，在平滑肌肉瘤异种移植物中以及在脂肪肉瘤和平滑肌肉瘤细胞系中研究了艾日布林。
结果
艾日布林在体外对所有六种研究的细胞系显示出抗增殖活性，50%抑制浓度值约为1 nmol/l，以及在体内对四种异种移植物具有显著的抗肿瘤活性。此外，艾日布林显着增强异种移植瘤的血液灌注，并诱导形态学变化和分化标志基因的上调。
结论
在临床前模型中，艾日布林对STS的各种组织病理学亚型显示出抗增殖活性。艾日布林还可能引起肿瘤血管重塑，增强肿瘤血液灌注并诱导肿瘤细胞分化。
BACKGROUND
Eribulin mesilate (eribulin), a first-in-class halichondrin B-based microtubule dynamics inhibitor, has been shown to promote vascular remodeling and reversal of epithelial-mesenchymal transition (EMT) apart from its antimitotic activity in breast cancer models.
MATERIALS AND METHODS
Anti-proliferative activity of eribulin was examined in vitro and in vivo in several human soft tissue sarcoma (STS) cell lines. To assess tumor blood perfusion and phenotypic changes, eribulin was investigated in a leiomyosarcoma xenograft and in vitro in liposarcoma and leiomyosarcoma cell lines.
RESULTS
Eribulin showed anti-proliferative activity in vitro against all six cell lines investigated, with 50% inhibitory concentration values of around 1 nmol/l, as well as significant antitumor activity against four xenografts in vivo. In addition, eribulin significantly enhanced tumor blood perfusion in xenografts and induced morphological changes and up-regulation of differentiation marker genes.
CONCLUSION
In pre-clinical models, eribulin showed anti-proliferative activity against a variety of histopathological subtypes of STS. Eribulin might also cause tumor vasculature remodeling to enhance tumor blood perfusion and induce tumor cell differentiation.