한빛사논문
- 조회540
Juyeon Seo1,2,3 · Minsu Park1,2,3 · Dongmi Ko1,2,3 · Seongjae Kim1,2,3 · Jung Min Park1,2,3 · Soeun Park1,2,3 · Kee Dal Nam1,3 · Lee Farrand4 · Jinsol Yang5 · Chaok Seok5,6 · Eunsun Jung1,3,7 · Yoon‑Jae Kim1,2,3,7 · Ji Young Kim1,3,7 · Jae Hong Seo1,2,3,7
1 Division of Medical Oncology, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 02841, Republic of Korea
2 Brain Korea 21 Program for Biomedical Science, Korea University College of Medicine, Korea University, Seoul 02841, Republic of Korea
3 Department of Biomedical Research Center, Korea University Guro Hospital, Korea University, Seoul 08308, Republic of Korea
4 Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5000, Australia
5 Galux Inc, Gwanak-Gu, Seoul 08738, Republic of Korea
6 Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea
7 Guro Hospital Campus, Korea University, 97 Gurodong-Gil, Guro-Guu, Seoul 08308, Republic of Korea
Corresponding authors : Correspondence to Eunsun Jung, Yoon-Jae Kim, Ji Young Kim or Jae Hong Seo.
Abstract
We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration signifcantly impeded BCSCenriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our fndings suggest that EBA may represent an efective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-06-19)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
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