Micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in tumor cells in an USP7/AKT/GSK-3β pathway-dependent manner

Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2023-12-18 DOI:10.1007/s00210-023-02903-w

{"title":"Micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in tumor cells in an USP7/AKT/GSK-3β pathway-dependent manner","authors":"","doi":"10.1007/s00210-023-02903-w","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>Breast cancer and osteosarcoma are common cancers in women and children, respectively, but ideal drugs for treating patients with breast cancer or osteosarcoma remain to be found. Micafungin is an antifungal drug with antitumor activity on leukemia. Based on the notion of drug repurposing, this study aims to evaluate the antitumor effects of micafungin on breast cancer and osteosarcoma in vitro and in vivo, and to elucidate the underlying mechanisms. Five breast cancer cell lines (MDA-MB-231, BT-549, SK-BR-3, MCF-7, and 4T1) and one osteosarcoma cell line (143B) were chosen for the in vitro studies. Micafungin exerted an inhibitory effect on the viability of all cell lines, and MCF-7 cells were most sensitive to micafungin among the breast cancer cell lines. In addition, micafungin showed an inhibitory effect on the proliferation, clone formation, and migration in MCF7 and 143B cells. The inhibitory effect of micafungin on the growth of breast cancer and osteosarcoma was further confirmed with xenograft tumor mouse models. To explore the underlying mechanisms, the effect of micafungin on epithelial-mesenchymal transition (EMT) was examined. As expected, the levels of matrix metalloproteinase 9 and vimentin in MCF-7 and 143B cells were notably reduced in the presence of micafungin, concomitant with the decreased levels of ubiquitin-specific protease 7 (USP7), p-AKT, and p-GSK-3β. Based on these observations, we conclude that micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in an USP7/AKT/GSK-3β pathway-dependent manner.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Naunyn-schmiedebergs Archives of Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s00210-023-02903-w","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Breast cancer and osteosarcoma are common cancers in women and children, respectively, but ideal drugs for treating patients with breast cancer or osteosarcoma remain to be found. Micafungin is an antifungal drug with antitumor activity on leukemia. Based on the notion of drug repurposing, this study aims to evaluate the antitumor effects of micafungin on breast cancer and osteosarcoma in vitro and in vivo, and to elucidate the underlying mechanisms. Five breast cancer cell lines (MDA-MB-231, BT-549, SK-BR-3, MCF-7, and 4T1) and one osteosarcoma cell line (143B) were chosen for the in vitro studies. Micafungin exerted an inhibitory effect on the viability of all cell lines, and MCF-7 cells were most sensitive to micafungin among the breast cancer cell lines. In addition, micafungin showed an inhibitory effect on the proliferation, clone formation, and migration in MCF7 and 143B cells. The inhibitory effect of micafungin on the growth of breast cancer and osteosarcoma was further confirmed with xenograft tumor mouse models. To explore the underlying mechanisms, the effect of micafungin on epithelial-mesenchymal transition (EMT) was examined. As expected, the levels of matrix metalloproteinase 9 and vimentin in MCF-7 and 143B cells were notably reduced in the presence of micafungin, concomitant with the decreased levels of ubiquitin-specific protease 7 (USP7), p-AKT, and p-GSK-3β. Based on these observations, we conclude that micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in an USP7/AKT/GSK-3β pathway-dependent manner.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

米卡芬净通过依赖 USP7/AKT/GSK-3β 通路的方式防止肿瘤细胞的 EMT，从而对乳腺癌和骨肉瘤产生抗肿瘤作用

摘要乳腺癌和骨肉瘤分别是妇女和儿童的常见癌症，但治疗乳腺癌和骨肉瘤患者的理想药物仍有待找到。米卡芬净是一种对白血病具有抗肿瘤活性的抗真菌药物。基于药物再利用的概念，本研究旨在评估米卡芬净在体外和体内对乳腺癌和骨肉瘤的抗肿瘤作用，并阐明其潜在机制。体外研究选择了五种乳腺癌细胞株（MDA-MB-231、BT-549、SK-BR-3、MCF-7 和 4T1）和一种骨肉瘤细胞株（143B）。结果表明，米卡芬净对所有细胞株的活力都有抑制作用，而在乳腺癌细胞株中，MCF-7 细胞对米卡芬净最为敏感。此外，米卡芬净对 MCF7 和 143B 细胞的增殖、克隆形成和迁移也有抑制作用。通过异种移植肿瘤小鼠模型，进一步证实了米卡芬净对乳腺癌和骨肉瘤生长的抑制作用。为了探究其潜在机制，研究人员检测了米卡芬净对上皮-间质转化（EMT）的影响。正如预期的那样，MCF-7 和 143B 细胞中基质金属蛋白酶 9 和波形蛋白的水平在有米卡芬净存在的情况下显著降低，同时泛素特异性蛋白酶 7 (USP7)、p-AKT 和 p-GSK-3β 的水平也降低了。基于这些观察结果，我们得出结论：米卡芬净通过USP7/AKT/GSK-3β通路依赖的方式防止EMT，从而对乳腺癌和骨肉瘤产生抗肿瘤作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Naunyn-schmiedebergs Archives of Pharmacology

自引率

0.00%

发文量