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<p>Cucurbitacin B (CuB), the tetracyclic triterpenoid compound belonging to cucurbitaceae family, demonstrates significant anticancer properties across various tumor types. However, its efficacy against glioblastoma (GBM), particularly in overcoming blood-brain barrier (BBB) and unique tumor microenvironment, remains a critical area of investigation. Our study reveals that CuB causes GBM cell apoptosis via STAT3/ROS/endoplasmic reticulum (ER) stress pathway. To enhance targeted delivery, we developed M@CuB-Lips, a novel formulation of CuB encapsulated in cancer cell membrane-coated liposomes. In vitro and in vivo experimental results verified targeted M@CuB-Lips delivery to brain tumor sites, demonstrating significant tumor inhibition and enhanced effector T-cell infiltration. These findings underscore CuB’s potential in GBM therapy, particularly through STAT3 suppression and ROS-ER Stress pathway activation, while M@CuB-Lips offers a promising strategy for targeted drug delivery.</p>

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Cucurbitacin B suppresses glioblastoma via the STAT3/ROS/endoplasmic reticulum stress pathway

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月27日

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  • Guangyao Lv,
  • Shanshan Sun,
  • Xueying Li,
  • Ruxia Han,
  • Shule Liu,
  • Mei Lu,
  • Xinfu Gao,
  • Jianqiao Zhang,
  • Wenwen Lv

摘要

Cucurbitacin B (CuB), the tetracyclic triterpenoid compound belonging to cucurbitaceae family, demonstrates significant anticancer properties across various tumor types. However, its efficacy against glioblastoma (GBM), particularly in overcoming blood-brain barrier (BBB) and unique tumor microenvironment, remains a critical area of investigation. Our study reveals that CuB causes GBM cell apoptosis via STAT3/ROS/endoplasmic reticulum (ER) stress pathway. To enhance targeted delivery, we developed M@CuB-Lips, a novel formulation of CuB encapsulated in cancer cell membrane-coated liposomes. In vitro and in vivo experimental results verified targeted M@CuB-Lips delivery to brain tumor sites, demonstrating significant tumor inhibition and enhanced effector T-cell infiltration. These findings underscore CuB’s potential in GBM therapy, particularly through STAT3 suppression and ROS-ER Stress pathway activation, while M@CuB-Lips offers a promising strategy for targeted drug delivery.