多药耐药是导致肺癌化疗失败的主要原因之一。许多研究表明通过非凋亡途径杀灭肿瘤细胞或下调MDR1基因表达可能规避肿瘤耐药。自噬是一种新的程序性细胞死亡方式，研究发现，诱导过度激活自噬可以杀灭肿瘤细胞。此外，自噬相关的PI3K/Akt和AMPK-mTOR两条重要信号通路与肿瘤的MDR1基因表达及耐药有关。最近研究发现AEG-1不仅通过AMPK-mTOR介导肿瘤细胞保护性自噬，还能通过PI3K/Akt上调肿瘤的MDR1基因表达，产生耐药性。雷公藤氯内酯醇T4具有毒性低药理活性高的特点。我们的前期研究发现T4能下调AEG-1的表达，诱导肺腺癌细胞A549及多药耐药细胞A549/DDP产生自噬性细胞死亡。本研究以A549及A549/DDP细胞和裸鼠皮下移植瘤为模型，观察T4通过AEG-1对肺癌自噬和耐药的影响，并探讨上述两条信号通路在其中的作用。本研究将为T4在多药耐药肺腺癌的治疗提供理论依据。

Tumor multidrug resistance is the main reason for the failure of chemotherapy of lung cancer.More and more studies have shown that killing tumor cells by non-apoptotic pathway or downregulating MDR1 gene may circumvent tumor resistance. Autophagy is a new kind of programmed cell death mode.The current studies show that excessive autophagic death can result in the death of tumor cells. Moreover,two important signal pathways of autophagy PI3K/Akt and AMPK-mTOR are associated with tumor multidrug resistance.Recently, some scholars have found that AEG-1 not only can induce protect autophagy of tumor cells by AMPK-mTOR pathway, but also can induce tumor multidrug resistance by upregulating MDR1 gene via PI3K/Akt pathway. Tripterygium extracts tripchlorolide T4 has low toxicity and high pharmacological activity. Our previous study showed that T4 can downregulate AEG-1, induce A549 and A549/DDP cells autophagy. In this study, multidrug-resistant lung adenocarcinoma cell line A549 and A549/DDP and nude mice xenograft tumor models were used to examined the role of T4 and AEG-1 in regulating autophagy and multidrug resistance in lung cancer and its mechanisms.This study will provide a theoretical basis for T4 in the treatment of multidrug-resistant lung adenocarcinoma.