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Co-delivery of shikonin and JQ1 inhibits triple-negative breast tumor progression and lung metastasis through inhibition of epithelial-mesenchymal transition and vasculogenic mimicry

文献类型：期刊论文

作者Xu, Xing-yu2,3; Kalambhe, Dipika Ramdas2,3; Yu, Yue2,3; Yu, Ling-xi2,3; Gu, Zhi-wen2,4; Jin, Xiao-ying2,3; Wang, Hui-yuan2; Huang, Yong-zhuo1,2,3,5
刊名ACTA PHARMACOLOGICA SINICA
出版日期2025-07-14
页码13
关键词shikonin JQ1 vasculogenic mimicry epithelial-mesenchymal transition mesoporous polydopamine nanoparticle pickering emulsion
ISSN号1671-4083
DOI10.1038/s41401-025-01605-8
英文摘要Triple-negative breast cancer (TNBC) is highly prone to lung metastasis, primarily driven by epithelial-mesenchymal transition (EMT) and vasculogenic mimicry (VM). Therefore, inhibiting EMT and VM represents a promising therapeutic strategy for TNBC. The immunosuppressive tumor microenvironment contributes substantially to poor treatment outcomes, with M2-type macrophages secreting excessive levels of TGF-beta that promote both EMT and VM. In this study, we proposed a combination therapy strategy involving shikonin (SHK) and JQ1 delivered via a mesoporous polydopamine-based Pickering emulsion (termed MPDA@PE). This formulation significantly suppressed tumor growth and lung metastasis by inducing apoptosis in TNBC and inhibiting TGF-beta-induced EMT and VM. Furthermore, MPDA@PE can be incorporated into a thermosensitive hydrogel for application in the prevention of TNBC recurrence and lung metastasis following surgical resection. These findings highlight a potential therapeutic approach for effective TNBC treatment.The combined administration of SHK and JQ1 inhibits both EMT and VM. This approach disrupts the nutrient supply in tumor tissues by blocking VM and suppresses tumor metastasis through EMT inhibition. Consequently, it demonstrates therapeutic efficacy against TNBC recurrence post-surgery and effectively limits lung metastasis.
WOS关键词SIGNALING PATHWAY ; CANCER ; MACROPHAGES ; MECHANISMS ; GROWTH ; CELLS
资助项目National Key Research and Development Program of China[2024YFA1210200] ; National Natural Science Foundation of China[82341232] ; Natural Science Foundation of Shanghai Municipal[24ZR1477500] ; High-level Innovative Research Institute[2021B0909050003] ; Department of Science and Technology of Guangdong Province ; Zhongshan Municipal Bureau of Science and Technology[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022011]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001528193600001
出版者NATURE PUBL GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/318819]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Wang, Hui-yuan; Huang, Yong-zhuo
作者单位1.Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan 528437, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
5.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Xing-yu,Kalambhe, Dipika Ramdas,Yu, Yue,et al. Co-delivery of shikonin and JQ1 inhibits triple-negative breast tumor progression and lung metastasis through inhibition of epithelial-mesenchymal transition and vasculogenic mimicry[J]. ACTA PHARMACOLOGICA SINICA,2025:13.
APA Xu, Xing-yu.,Kalambhe, Dipika Ramdas.,Yu, Yue.,Yu, Ling-xi.,Gu, Zhi-wen.,...&Huang, Yong-zhuo.(2025).Co-delivery of shikonin and JQ1 inhibits triple-negative breast tumor progression and lung metastasis through inhibition of epithelial-mesenchymal transition and vasculogenic mimicry.ACTA PHARMACOLOGICA SINICA,13.
MLA Xu, Xing-yu,et al."Co-delivery of shikonin and JQ1 inhibits triple-negative breast tumor progression and lung metastasis through inhibition of epithelial-mesenchymal transition and vasculogenic mimicry".ACTA PHARMACOLOGICA SINICA (2025):13.

入库方式： OAI收割

来源：上海药物研究所

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