主题：之一：《柳叶刀》上的中医 -- 良金百辟

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–α expression in the intestine, and proinflammatory cytokine concentrations in plasma. Chemical constituents of PHY906 potently inhibited nuclear factor κB, 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.

The use of complementary and alternative medicine (CAM) has become a core component of the daily challenges faced when treating cancer patients. PHY906 is a formulation of four herbal compounds traditionally used to treat nausea, vomiting, cramping, and diarrhea. Diarrhea is one of the major side effects of the cancer drug irinotecan. In this issue of Science Translational Medicine, Lam and colleagues report that administration of PHY906 with irinotecan in a mouse model of colon cancer resulted in a synergistic reduction in tumor burden, maintenance of body weight, and stem cell regeneration in the intestinal mucosa. Yet when considering CAM use in the treatment of cancer patients, one must take into account reproducibility of preclinical findings in clinical practice, quality assurance of herbal products, and potential toxicities associated with alternative therapies.