肝癌是最常见的恶性肿瘤之一。5-氟尿嘧啶（5-FU）是一个常用肝癌化疗药物，但其临床疗效差且有明显的毒性。含黄芪或五味子的中药复方常被用作肝癌化疗的辅助药物。本课题组前期研究发现，由黄芪和五味子组成的方剂“芪味丸”（QWW）具有协同5-FU抗肝癌的作用，并能减轻5-FU的毒性。机制研究发现，QWW及QWW/5-FU联用可抑制PDGFR-β和STAT3（PDGFR-β下游信号传导分子）的磷酸化/激活。基于此，我们推测抑制PDGFR-β/STAT3信号通路在QWW与5-FU协同抗肝癌中起重要作用。本项目拟1）在细胞模型上研究抑制PDGFR-β/STAT3通路在QWW/5-FU联用抗肝癌作用中的贡献；2）在动物模型上进一步研究QWW/5-FU联用抗肝癌的作用；3）在多种人源肝癌细胞株上研究QWW/5-FU联用抗肝癌的活性。该研究将为开发QWW成为5-FU治疗肝癌的辅助药物提供药理学依据。

Liver cancer is one of the most common malignant neoplasms. 5-fluorouracil (5-FU) is a frequently used therapeutic drug for liver cancer, but its clinical efficacy is poor and its toxicities are evident. Huangqi (Astragali Radix) or Wuweizi (Schisandrae chinensis Fructus) based Chinese medicine prescriptions are commonly used as adjuvants in liver cancer chemotherapies. Our preliminary studies demonstrated that Qi-Wei-Wan (QWW for short) comprising Huangqi and Wuweizi synergizes the anti-liver cancer effects and reduces the toxicities of 5-FU. Mechanistic studies showed that QWW alone or in combination with 5-FU suppresses the phosphorylation/activation of PDGFR-β and STAT3 (a downstream molecular of PDGFR-β). We hypothesize that inhibiting the PDGFR-β/STAT3 pathway plays an important role in the synergistic anti-liver cancer effects of QWW and 5-FU. To prove this hypothesis, we propose to 1) determine the contribution of inhibiting the PDGFR-β/STAT3 pathway in the anti-liver cancer effects of the QWW/5-FU combination in cell models; 2) further determine the anti-liver cancer effects of the QWW/5-FU combination in animal models; 3) determine the anti-liver cancer effects of the QWW/5-FU combination in more liver cancer cells. Findings of this study will provide a pharmacological basis for developing QWW as an adjuvant of 5-FU in liver cancer management.