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Cancer research

Zhenqi Fuzheng Granule Targets SCFAs-GPR109A Axis to Enhance PD-1 Antibody Efficacy in Colorectal Cancer

Strategic Insights

— 2 min read

Researchers at the Tianjin University of Traditional Chinese Medicine have made a groundbreaking discovery in the field of oncology, leveraging the power of traditional Chinese medicine to enhance the efficacy of PD-1 antibody treatment in colorectal cancer. The study, published in the journal Phytomedicine, reveals that Zhenqi Fuzheng Granule (ZQFZ), a clinically approved herbal prescription, exerts its antitumor effects by modulating the gut microbiota, increasing short-chain fatty acids (SCFAs) production, and activating the GPR109A pathway. This study provides new insights into the immunometabolic mechanism of ZQFZ and its potential to enhance PD-1 antibody efficacy in colorectal cancer.

Key Takeaways:

  • Zhenqi Fuzheng Granule (ZQFZ) is a clinically approved herbal prescription used to treat colorectal cancer, and its mechanistic underpinnings have been elusive until now.
  • ZQFZ reshapes the gut microbiota, increasing SCFAs production, particularly butyrate, and activates the GPR109A pathway, leading to downregulation of the AKT/mTOR/HIF-1α signaling axis.
  • The combination of ZQFZ and PD-1 antibody exerts the most pronounced antitumor effects, inhibiting tumor growth, and remodeling the immune microenvironment.
  • Sodium butyrate (NaB), the major gut microbial metabolite of ZQFZ, suppresses colorectal cancer cell viability and induces apoptosis by inhibiting glycolysis and the AKT/mTOR/HIF-1α pathway.
  • The study provides a novel integrated mechanism for ZQFZ-enhanced PD-1 antibody efficacy via the gut microbiota-SCFAs-GPR109A axis, and NaB-mediated glycolysis inhibition under hypoxia further confirms its immunometabolic mechanism against CRC.
  • ZQFZ-derived fecal microbiota transplantation (FMT) significantly inhibits tumor growth and remodulates the immune microenvironment by reducing myeloid-derived suppressor cells (MDSCs) and enhancing M1 macrophages and CD8 T cell infiltration.
  • The study suggests that ZQFZ and NaB may interact synergistically to inhibit glycolysis, mitochondrial biogenesis, and the AKT/mTOR/HIF-1α signaling pathway, offering a new therapeutic strategy for CRC treatment.

Statistics:

  • Seven major compounds were identified in ZQFZ using LC-MS/MS and UPLC-MS/MS, including Adenosine (0.87mg/g), Salidroside (0.11 mg/g), Astragaloside IV (0.07 mg/g), Calycosin (0.03 mg/g), Formononetin (6.7 mg/g), Chlorogenic acid (1.4 mg/g), and Apigenin (0.5 mg/g).
  • The combination of ZQFZ and PD-1 antibody inhibited tumor growth by 60%, whereas single treatment with ZQFZ or PD-1 antibody inhibited tumor growth by 40% and 50%, respectively.
  • ZQFZ-derived FMT significantly inhibited tumor growth by 70%, suppressed glycolysis-related markers (PKM2, GLUT1, HIF-1α, LDHA) by 50%, and remodeled the immune microenvironment by reducing MDSCs by 30%.

Sources:

  • Zhenqi Fuzheng Granule targets the SCFAS-GPR109A axis to enhance PD-1 antibody efficacy via immunometabolic remodeling in colorectal cancer. Phytomedicine, 2025;148:157312.
  • NewsRx. Recent Studies from Tianjin University of Traditional Chinese Medicine Add New Data to Colon Cancer (Zhenqi Fuzheng Granule targets the SCFAS-GPR109A axis to enhance PD-1 antibody efficacy via immunometabolic remodeling in colorectal cancer). Cancer Weekly. October 14, 2025; p 3210.

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