癌症干细胞
癌症研究
三阴性乳腺癌
转移
氯硝柳胺
人口
醛脱氢酶
干细胞
医学
车站3
癌症
化学
细胞凋亡
生物
乳腺癌
内科学
细胞生物学
生物化学
基因
环境卫生
生态学
作者
Ji Hyeon Kim,Soeun Park,Eunsun Jung,Jin Woo Shin,Yoon-Jae Kim,Ji Young Kim,Jonathan L. Sessler,Jae Hong Seo,Jong Seung Kim
标识
DOI:10.1073/pnas.2304081120
摘要
Chemotherapy typically destroys the tumor mass but rarely eradicates the cancer stem cells (CSCs) that can drive metastatic recurrence. A key current challenge is finding ways to eradicate CSCs and suppress their characteristics. Here, we report a prodrug, Nic-A, created by combining a carbonic anhydrase IX (CAIX) inhibitor, acetazolamide, with a signal transducer and transcriptional activator 3 (STAT3) inhibitor, niclosamide. Nic-A was designed to target triple-negative breast cancer (TNBC) CSCs and was found to inhibit both proliferating TNBC cells and CSCs via STAT3 dysregulation and suppression of CSC-like properties. Its use leads to a decrease in aldehyde dehydrogenase 1 activity, CD44high/CD24low stem-like subpopulations, and tumor spheroid-forming ability. TNBC xenograft tumors treated with Nic-A exhibited decreased angiogenesis and tumor growth, as well as decreased Ki-67 expression and increased apoptosis. In addition, distant metastases were suppressed in TNBC allografts derived from a CSC-enriched population. This study thus highlights a potential strategy for addressing CSC-based cancer recurrence.
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