基于mTORC1调节自噬相关复合体Beclin1/Bcl-2研究芪玉三龙汤抗非小细胞肺癌机制

非小细胞肺癌（NSCLC）发病多，死亡率高，目前主要采用化疗、靶向及免疫疗法。中医复方具有多靶点、毒副作用小等特点，我们对益气养阴、化痰祛瘀、解毒抗癌的芪玉三龙汤临床研究表明该方可不同程度改善肺癌患者临床症状，实验研究发现该方可下调自噬调节基因mTOR表达并影响癌组织超微结构，而mTORC1是Beclin1介导的细胞自噬性死亡的主要抑制因子。因此提出芪玉三龙汤可通过抑制mTORC1水平促进Beclin1/Bcl2复合体介导的细胞自噬性死亡达到抑制肿瘤的假说。本项目拟体内采用肺癌移植瘤模型，进一步明确该方抑制肿瘤与mTORC1调节Beclin1/Bcl2复合体介导自噬的相关性；体外采用肺癌细胞株模型，运用基因干扰、外源基因表达等技术，研究该方对Beclin1及其他自噬基因表达、自噬小体形成及细胞死亡的影响，从而揭示该方抗肺癌的分子机制，为现代生物学角度优化芪玉三龙汤治疗肺癌提供科学依据。

Non-small cell lung cancer (NSCLC) has a high incidence and high mortality. Currently，chemotherapy，targeted-therapy and immunotherapy are the primary treatment. Chinese medicine prescription has the characteristics of multiple targets and small side effects. Our previous clinical research showed that Qiyusanlong Decoction（QYSL）with tonifying qi and yin，dissipating phlegm and blood stasis，detoxification and anticancer could improve clinical symptoms of lung cancer patients. Meanwhile，experimental study found that the recipe could reduce mTOR expression and influence ultrastructure of cancer tissues. mTORC1，is the main inhibitor of Beclin1 mediated autophagy death. So，we come up with hypothesis that QYSL can inhibit lung caner through controlling mTORC1 and promoting Beclin1/Bcl-2 complex mediated lung caner autophagy death. This project will adopt transplantation lung tumors model in vivo to further determine correlation between inhibitory tumor and mTORC1 regulating Beclin1/Bcl-2 mediated autophagy. In vitro，lung cancer cell line model will be used and gene interference，exogenous gene expression technology will be adopted to investigate effects of QYSL on Beclin1，another autophagy gene expression，autophagosome and cell death. Thus，it will reveal the molecular mechanism of anti-lung caner about QYSL and provide scientific basis for optimizing QYSL treatment for lung cancer from modern biology perspective.