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<p>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-β 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-β-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.</p><p></p>

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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

  • 期刊论文

  • 发表日期：

    2025年7月14日

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  • Xing-yu Xu,
  • Dipika Ramdas Kalambhe,
  • Yue Yu,
  • Ling-xi Yu,
  • Zhi-wen Gu,
  • Xiao-ying Jin,
  • Hui-yuan Wang,
  • Yong-zhuo Huang

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-β 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-β-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.