Synergistic antitumor effects of S-1 with eribulin in vitro and in vivo for triple-negative breast cancer cell lines.
Synergistic antitumor effects of S-1 with eribulin in vitro and in vivo for triple-negative breast cancer cell lines.
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DOI：
10.1186/2193-1801-3-417
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Nishio K
中科院分区：
文献类型：
--
作者：
Terashima M;Sakai K;Togashi Y;Hayashi H;De Velasco MA;Tsurutani J;Nishio K
三阴性乳腺癌（TNBC）具有较高的复发率和远处转移发生率以及较差的预后，而有效的治疗策略仍有待制定。寻找 TNBC 的有效治疗方法已刻不容缓。我们检查了 S-1（或体外研究中的 5-FU）和艾日布林组合在 TNBC 细胞系中的作用。使用组合指数和等效线图在四种 TNBC 细胞系（MDA-MB-231、MDA-MB-468、BT-549 和 MX-1）中检查了组合的体外效果。此外，我们还评估了该组合在 MDA-MB-231 肿瘤异种移植模型中的效果。在三种 TNBC 细胞系（MDA-MB-231、MDA-MB-468 和 MX-1）中观察到协同效应，并且在一项体内研究中，S-1 和艾日布林的组合与单独使用 S-1 或艾日布林相比，产生显着更高的抗肿瘤效果。 5-FU 诱导 TNCB 细胞系中的上皮-间质转化 (EMT) 变化，上皮标记物表达减少和间质标记物表达增加支持这一点。同时，TGF-β 诱导 TNBC 细胞系发生 EMT 变化，并降低对 5-FU 的敏感性。该结果表明 5-FU 诱导的 EMT 变化降低了对 5-FU 的敏感性。相比之下，艾日布林在 TNBC 细胞系中诱导间充质上皮转化 (MET)。 5-FU 诱导的 EMT 表型也被艾日布林取消。我们证明，S-1 (5-FU) 和艾日布林的组合通过艾日布林的 MET 诱导对 TNBC 细胞系发挥协同作用。因此，这种联合疗法可能是TNBC的潜在治疗选择。
Triple-negative breast cancer (TNBC) is associated with a higher incidence of recurrence and distant metastasis and a poor prognosis, whereas effective treatment strategies remain to be established. Finding an effective treatment for TNBC has become imperative. We examined the effect of the combination of S-1 (or 5-FU in an in vitro study) and eribulin in TNBC cell lines. The in vitro effect of the combination was examined in four TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-549 and MX-1) using a combination index and isobolograms. In addition, we assessed the effect of the combination in an MDA-MB-231 tumor xenograft model. A synergistic effect was observed in three TNBC cell lines (MDA-MB-231, MDA-MB-468, and MX-1), and in an in vivo study, the combination of S-1 and eribulin resulted in significantly higher antitumor effects compared with S-1 or eribulin alone. 5-FU induced epithelial-mesenchymal transition (EMT) change in the TNCB cell line, as supported by the decreased expression of epithelial marker and the increased expression of mesenchymal markers. Meanwhile, TGF-beta induced EMT changes in a TNBC cell line and decreased the sensitivity to 5-FU. This result suggests that 5-FU-induced EMT changes reduce the sensitivity to 5-FU. In contrast, eribulin induced a mesenchymal-epithelial transition (MET) in a TNBC cell line. The EMT phenotype induced by 5-FU was also canceled by eribulin. We demonstrate that the combination of S-1 (5-FU) and eribulin exerts a synergistic effect for TNBC cell lines through MET-induction by eribulin. Therefore, this combination therapy may be a potential treatment option for TNBC.
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