The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity

Sci Transl Med. 2010 Aug 18;2(45):45ra59. doi: 10.1126/scitranslmed.3001270.


PHY906, a four-herb Chinese medicine formula first described 1800 years ago, decreases gastrointestinal toxicity induced by the chemotherapeutic drug CPT-11 (irinotecan), as shown in a phase I/II clinical study. Similarly, in a murine colon 38 allograft model, PHY906 increased the antitumor activity of CPT-11 while decreasing animal weight loss caused by CPT-11. Here, we have further examined the effect of PHY906 on the intestinal toxicity caused by CPT-11 in mice. PHY906 did not protect against the initial DNA damage and apoptosis triggered by CPT-11 in the intestine, but by 4 days after CPT-11 treatment, PHY906 had restored the intestinal epithelium by promoting the regeneration of intestinal progenitor or stem cells and several Wnt signaling components. PHY906 also potentiated Wnt3a activity in human embryonic kidney-293 cells. Furthermore, PHY906 exhibited anti-inflammatory effects in mice by decreasing the infiltration of neutrophils or macrophages, tumor necrosis factor-alpha expression in the intestine, and proinflammatory cytokine concentrations in plasma. Chemical constituents of PHY906 potently inhibited nuclear factor kappaB, cyclooxygenase-2, and inducible nitric oxide synthase. Our results show that the herbal medicine PHY906 can counteract the toxicity of CPT-11 via several mechanisms that act simultaneously.

Trial registration: NCT00730158.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Apoptosis / drug effects
  • Biomarkers, Tumor / metabolism
  • Bromodeoxyuridine / metabolism
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / toxicity
  • Cell Proliferation / drug effects
  • DNA Damage
  • Drugs, Chinese Herbal / pharmacology*
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / pathology*
  • Gastrointestinal Tract / physiopathology
  • Glucuronidase / metabolism
  • Humans
  • Inflammation / pathology
  • Irinotecan
  • Medicine, Chinese Traditional*
  • Mice
  • Proliferating Cell Nuclear Antigen / metabolism
  • Recovery of Function / drug effects
  • Signal Transduction / drug effects
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Transplantation, Homologous
  • Weight Loss / drug effects
  • Wnt Proteins / metabolism
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin / metabolism


  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Drugs, Chinese Herbal
  • PHY 906
  • Proliferating Cell Nuclear Antigen
  • WNT3A protein, human
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • beta Catenin
  • Irinotecan
  • Glucuronidase
  • Bromodeoxyuridine
  • Camptothecin

Associated data