芪玉三龙汤通过PTEN/mTOR/STAT3信号通路诱导M2/M1巨噬细胞极化重塑NSCLC肿瘤微环境的机制研究

“元气化生异常、内生瘤毒、毒生病络”是肺癌发生的重要病因，“扶正解毒通络”为肺癌的重要治法。非小细胞肺癌（NSCLC）肿瘤微环境中浸润的巨噬细胞主要为M2型。本团队前期研究发现具有“益气养阴、化痰祛瘀、解毒消积”功效的抗肺癌验方芪玉三龙汤能诱导巨噬细胞极化为M1型且抑制T细胞表面抑制性分子的表达。PTEN/mTOR/STAT3信号通路与巨噬细胞极化密切相关，据此我们提出芪玉三龙汤可以通过调控该信号通路诱导M2/M1巨噬细胞极化从而介导T细胞活化，重塑NSCLC肿瘤微环境的假说。本研究拟采用流式细胞术、ELISA、RT-PCR、Western blot、免疫荧光等技术，从分子、细胞及动物水平，多层面研究“芪玉三龙汤-巨噬细胞极化-肿瘤微环境重塑”免疫应答轴线，揭示该方通过该免疫应答轴线介导机体免疫应答激活从而发挥抗肿瘤作用的机制，为该方重塑肿瘤微环境及“扶正解毒通络”理论提供科学依据。

"Abnormal metaplasia of Qi,endogenous tumor toxin and toxic pathogenic collaterals" is the important cause of lung cancer,"strengthening,detoxifying and unblocking collaterals" is an important treatment method for lung cancer.Macrophages infiltrated in tumor microenvironment of Non-small cell lung cancer (NSCLC) are mainly M2 type.In our team's previous research,we found that Qi Yu San Long Decoction,an anti lung cancer prescription,which has the effects of "benefiting Qi and nourishing Yin,resolving phlegm and removing blood stasis,detoxifying and eliminating accumulation",could induce macrophage polarization to M1 type and inhibit the expression of inhibitory molecules on the surface of T cells. PTEN/mTOR/STAT3 signal pathway is closely related to macrophage polarization.Therefore, we propose the hypothesis that Qi Yu San Long Decoction can induce the polarization of M2/M1 macrophages by regulating the signal pathway,thus mediate the activation of T cells and remodel the tumor microenvironment of NSCLC. In this research,flow cytometry,ELISA,RT-PCR,Western blot and immunofluorescence will be used to study the immune response axis of "Qi Yu San Long Decoction-macrophage polarization-tumor microenvironment remodeling" from molecular,cellular and animal levels.As a result,the mechanism of the prescription's anti-tumor effect via mediating immune response activation through the immune response axis can be revealed.We can also provide a scientific basis for the prescription’s remodeling of tumor microenvironment and the theory of "strengthening, detoxifying and unblocking collaterals".