Traditional medicine Bazi Bushen potentiates immunosurveillance of senescent liver cancer cells via cGAS-STING signaling activation in macrophages

  • Cancer Lett. 2025 Feb 8:217544. doi: 10.1016/j.canlet.2025.217544.
Fuxue Xing  1 ,  Hongwei Lv  2 ,  Wei Xiang  1 ,  Liang Wang  3 ,  Qianni Zong  3 ,  Guishuai Lv  3 ,  Chunying Liu  3 ,  Qiyu Feng  4 ,  Hongyang Wang  5 ,  Wen Yang  6
Affiliations
  • 1. Department of Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China.
  • 2. Department of Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China; National Center for Liver Cancer, Naval Medical University, Shanghai 201805, China; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Naval Medical University, Shanghai 200438, China; Shanghai Key Laboratory of Hepato-biliary Tumor Biology, Shanghai 200438, China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Shanghai 200438, China.
  • 3. National Center for Liver Cancer, Naval Medical University, Shanghai 201805, China; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Naval Medical University, Shanghai 200438, China.
  • 4. Department of Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: [email protected].
  • 5. Department of Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China; National Center for Liver Cancer, Naval Medical University, Shanghai 201805, China; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Naval Medical University, Shanghai 200438, China; Shanghai Key Laboratory of Hepato-biliary Tumor Biology, Shanghai 200438, China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Shanghai 200438, China. Electronic address: [email protected].
  • 6. Department of Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China; National Center for Liver Cancer, Naval Medical University, Shanghai 201805, China; International Co-operation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Naval Medical University, Shanghai 200438, China; Shanghai Key Laboratory of Hepato-biliary Tumor Biology, Shanghai 200438, China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, Ministry of Education, Shanghai 200438, China. Electronic address: [email protected].
PMID: 39929434 DOI: 10.1016/j.canlet.2025.217544
Abstract

Senescent Cancer cells often evade immune clearance to exert profound effects on Cancer progression and therapy resistance. Improving immunosurveillance to eliminate senescent Cancer cells is a crucial measure to enhance anti-cancer therapy. Bazi Bushen (BZBS) is a traditional medicine with the function of relieving fatigue and delaying ageing, but its role in tumor treatment remains poorly understood. Herein, we find that BZBS promotes immunosurveillance of both chemotherapy- and oncogene-induced senescent liver Cancer cells, further leading to enhanced chemotherapy efficacy and dramatic tumor repression in mice. Mechanistically, BZBS induces mitochondrial DNA leakage by mitochondrial damage to further activate cGAS-STING signaling in macrophages. Subsequently, cGAS-STING signaling activation in macrophages recruits CD8+ T cells into tumor and promotes the anti-tumor activity of CD8+ T cells to eradicate senescent Cancer cells. Furthermore, host STING is responsible for BZBS-mediated immunosurveillance of senescent liver Cancer cells in mice. Therefore, our findings unveil the role of traditional medicine BZBS in activating cGAS-STING signaling and potentiating senescence immunosurveillance to enhance anti-cancer therapy.

Keywords
Bazi Bushen; cGAS-STING signaling; immunosurveillance; liver cancer; macrophage; senescence.
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