化疗是治疗非小细胞肺癌的主要手段，但即使应用一线药物吉西他滨，患者的中位生存期也仅8个月，且伴随明显的骨髓抑制和肾毒性等副作用。当归补血汤联合吉西他滨治疗，可显著提高患者免疫功能、缓解毒副作用，延长生存时间。药物相互作用普遍存在，当归补血汤中黄芪和当归的主要活性成分分别对吉西他滨耐药相关蛋白有调节作用，但当归补血汤和吉西他滨是否存在相互作用、减毒增效机制如何发挥均未见报道。本项目拟从动物和细胞两水平，采用联用技术分析两药联用前后，主要活性成分在体内、外的药代动力学过程，研究药物相互作用；通过测定两药联用前、后，荷瘤小鼠各组织、肺癌细胞和耐药细胞中吉西他滨转运体和代谢酶的表达及活力，研究当归补血汤对吉西他滨代谢酶/转运体调控机制和逆转耐药机制，并结合药效、毒性评价和细胞因子分析，最终揭示当归补血汤与吉西他滨的增效减毒机制，为临床合理用药提供科学依据，并为其他中西药联用抗肿瘤机制研究提供思路。

Chemotherapy, a major treatment for non-small cell lung cancer (NSCLC), with median survival time (MST) of 8 months, leads to obvious side effect like myelosuppression and nephrotoxicity by using first-line drugs as gemcitabine. When gemcitabine was accompanied with Danggui buxue tang, the patients’ immunity improved and side effects alleviated, thus enhancing tolerance and prolonging survival time. Herb-drug interaction is ubiquitous，and the important proteins P-gp and GST-Pi could be regulated by the main active components in Astragalus membranaceus and Angelica sinensis, respectively. Yet it still remains unknown whether there is a herb-drug interaction, and how the interaction works between Danggui buxue tang and gemcitabine. Therefore, this project will compare pharmacokinetics of the major active components of gemcitabine and Danggui buxue tang with these two drugs administrated alone or combined, by hyphenated techniques on tumor-bearing mice and lung cancer cells, to study the influences on the physiological disposition. Comparing the expression and the activity of metabolic enzymes (dCK, CDA, GST-Pi) and transporters (hENT, hCNT, P-gp) on tissues, A549 cells and A549/Gem cells in different administration groups, to study the regulation mechanism, as well as analyzing the drug efficacy, toxicity and cytokine, will clarify the mechanism of efficacy enhancement and toxicity reduction of herb-drug combination. This work will not only provide scientific evidence for the clinical efficiency, but also guide rational usage of herb-drug combination, which facilitate further studies for anti-tumor mechanism of herb-drug combination.