Herbal formula enhances 5-fluorouracil activity through suppression of thymidylate synthase

Traditional Chinese herbal medicine(TCM) has been shown to enhance the efficacy of standard anticancer agents. However, there are only a limited number of well-controlled preclinical and clinical studies documenting the potential benefit of TCM. OBJECTIVE To identify biologically active formulas that were effective against colorectal cancer(CRC)by screening TCM formulas in in vitro and in vivo animal models. METHODS Cell growth assays, cell cycle analysis,immunoblot analysis and q RT-PCR were performed to investigate the mechanism(s) of action of the formulason human CRC cells. In vivo animal models were used to evaluate the antitumor activity of formulasalone and in combination with5-FU. RESULTS We identified Huangqin Gegen Tang(HQGGT) which suppressed the in vivo growth of human CRC HT-29 xenografts. HQGGT significantly inhibited the growth of CRC cell lines. HQGGT enhanced the cytotoxicity of5-FU against human 5-FU-resistant cells(H630 R1) and mouse colon cancer cells(MC38). This synergy was the result of suppression of thymidylate synthase expression by HQGGT. HQGGT significantly enhanced the antitumor effect of5-FU in mice bearing MC38 xenografts. Ongoing studies have identified Huangqin as the herb responsible for TS inhibition. CONCLUSION These findings provide support for the potential role of HQGGT as a novel modulator of fluoropyrimidine chemotherapy for CRC treatment.