Eribulin mesylate-induced c-Fos upregulation enhances cell survival in breast cancer cell lines

Eribulin mesylate-induced c-Fos upregulation enhances cell survival in breast cancer cell lines
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甲磺酸艾日布林诱导的 c-Fos 上调可增强乳腺癌细胞系的细胞存活率

DOI:
10.1016/j.bbrc.2020.03.042
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发表时间:
2020
影响因子:
3.1
通讯作者:
Itou Junji
Itou Junji
中科院分区:
生物学4区
文献类型:
--
作者:
Tanaka Sunao;Ishii Tomoko;Sato Fumiaki;Toi Masakazu;Itou Junji

文献摘要

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抗癌剂用于癌症治疗。对药剂治疗的生物学反应的研究有助于其有效使用。甲磺酸艾日布林(eribulin mesylate)是一种抗癌剂。在这项研究中,我们发现,c-Fos上调响应艾日布林治疗的三阴性乳腺癌细胞系MDA-MB-231和HCC 70,这具有低艾日布林敏感性。c-Fos表达在其他研究的细胞系中没有上调,包括高艾日布林敏感性细胞。我们假设c-Fos上调与艾日布林敏感性降低有关,因此使用了c-Fos抑制剂T-5224。在MDA-MB-231和HCC 70细胞中,在细胞生长测定、细胞死亡测定和小鼠异种移植肿瘤模型中,艾日布林和T-5224的联合治疗显示出比单独用艾日布林治疗更强的抗癌作用,而单独的T-5224显示出无抗癌作用。这些结果表明,T-5224可能增强艾日布林的抗癌作用。我们的发现有助于改善癌症治疗。
Anticancer agents are used for cancer therapy. Studies on the biological response to treatment with an agent facilitate its effective use. Eribulin mesylate (eribulin) is an anticancer agent. In this study, we found that c-Fos is upregulated in response to eribulin treatment in the triple-negative breast cancer cell lines MDA-MB-231 and HCC70, which have low eribulin sensitivity. c-Fos expression was not upregulated in other cell lines investigated, including high eribulin-sensitive cells. We hypothesized that c-Fos upregulation is involved in low eribulin sensitivity and thus used the c-Fos inhibitor, T-5224. In MDA-MB-231 and HCC70 cells, combined treatment with eribulin and T-5224 showed a stronger anticancer effect than treatment with eribulin alone in cell growth assays, cell death assays and a mouse xenograft tumor model, whereas T-5224 alone showed no anticancer effect. These results suggest that T-5224 may enhance the anticancer effect of eribulin. Our findings contribute to the improvement of cancer therapy.