云南肺腺癌全球高发，就诊时多处晚期，传统治疗获益较少，分子靶向治疗可延长患者预后。gefitinib是肺腺癌的主要靶点，多在治疗12-18月后发生获得性耐药。我们研究发现DHA能在体内外增加肺腺癌细胞系对gefitinib敏感性。结合DHA抗疟机制及生物信息学分析，进一步研究发现，DHA可抑制糖酵解关键酶PKM2和LDHA活性，降低ATP及乳酸产量。而敲减PKM2可增强肺腺癌细胞对gefitinib的敏感性，增加gefitinib和TK之间的亲和力。由此，我们提出DHA增加gefitinib敏感性可能的作用机制：DHA抑制糖酵解关键酶PKM2和LDHA活性，抑制糖酵解，阻断EGFR下游通路，增加gefitinib敏感性。本项目拟进一步采用酶活性检测等技术，旨在获得DHA干预糖酵解关键酶组增强gefitinib敏感性治疗肺腺癌的证据，为青蒿类药物增敏提供科学依据。

Lung adencarcinoma cancer has a globally high morbidity rate in Yunnan Province. The approach to treatment is often late, and outcomes are suboptimal with traditional treatment. Molecular targeted therapy can promote the prognosis of patients. Gefitinib is the main target of NSCLC, and acquired drug resistance often occurred at 12-18 months after the treatment. We found that DHA can enhance the sensitivity of lung adenocarcinoma cell lines to Gefitinib in vivo and in vitro. Combined with DHA antimalarial mechanism and bioinformatics analysis, further study found that DHA can inhibit the activity of glycolysis key enzymes PKM2 and LDHA, thus reducing the ATP and lactic acid production. The knock-down of PKM2 could enhance the sensitivity of Gefitinib to lung adenocarcinoma cells and increase the affinity between Gefitinib and TK. Therefore, we propose the potential mechanism of how DHA increase the Gefitinib sensitivity, that DHA inhibits the activities of PKM2 and LDHA in the key enzymes of glycolysis, enhances the affinity between Gefitinib and TK, and blocks EGFR downstream pathways, then the sensitivity enhanced. In this study, we are going to use methodologies like enzyme activity assays, to obtain the solid evidence that DHA increases the Gefitinib treatment sensitivity by interfering with key enzymes of glycolysis, and to provide the scientific basis for the sensitization effect of Artemisinin drugs.