基于CD11b+髓系细胞分化探究益气活血法重塑肺转移前微环境防止肺癌转移的效应机制

防止肺癌复发转移是临床急需解决的关键问题，中医药防治肿瘤优势在于有效预防复发转移。调控髓系细胞分化重塑肺转移前微环境是防止肺癌转移关键机制。课题组研究发现具有益气活血作用的双参颗粒可减少荷瘤小鼠肺中MDSCs数量，抑制肺特异性的招募因子TGF-β、GM-CSF含量，提示双参颗粒可调控髓系细胞分化参与肺癌转移微环境重塑。基于前期积累和双参颗粒防治肺癌有效的前提下，本课题拟以CD11b+BMDCs分化为切入点，以TNF-α/IL-6-NF-κB/STAT3募集TDSFs为靶点，建立骨髓GFP+、稳定转染荧光素酶LL/2-luc-M38Lewis肺癌小鼠模型与单细胞悬液、CD11b+BMDCs、Lewis肺癌细胞共培养模型，观察益气活血法（双参颗粒）干预肺转移前微环境对肺转移结局影响，以期揭示益气活血法调控肺转移前微环境防止肺癌转移的效应机制，为中医药防治肺癌转移提供证据支撑。

Preventing recurrence and metastasis of lung cancer is a key issue that needs to be urgently addressed in clinical practice. The advantage of traditional Chinese medicine in preventing and treating tumors lies in the effective prevention of recurrence and metastasis. Regulating myeloid cell differentiation and remodeling the microenvironment before lung metastasis is a key molecular mechanism to prevent lung cancer metastasis. Previous results show that Shuangshen granules can reduce the number of Myeloid-derived suppressor cells (MDSCs) in lungs of tumor-bearing mice, inhibit the lung-specific recruitment factors TGF-β and GM-CSF level, which suggests that Shuangshen granules can regulate myeloid cell differentiation and participate in the remodeling of lung cancer metastasis microenvironment. Based on these previous findings, this project intends to take the differentiation of CD11b + BMDCs as the entry point, and target specific TNF-α / IL-6-NF-κB / STAT3 to recruit TDSFs as the target to establish bone marrow GFP + and stably transfect luciferase LL / 2-luc -M38 Lewis lung cancer mouse model with lung single cell suspension, CD11b+BMDCs, and Lewis lung cancer cell co-culture models, to observe the effect of supplemeting Qi and activating Blood circulation method intervention on lung metastasis in order to reveal the benefits of lung metastasis, and supply evidence of prevention lung cancer metastasis with TCM.