Experiment study on Yiqi Fuzheng Prescription in anti⁃lung cancer metastasis by regulating the polarization of tumor associated macrophages

Yichen LIU; Jun ZHU; Guolei ZHANG; Li HAN; Zhihong FANG

doi:10.16305/j.1007-1334.2022.2104044

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Experiment study on Yiqi Fuzheng Prescription in anti⁃lung cancer metastasis by regulating the polarization of tumor associated macrophages

更新时间：2022-07-10

- Experiment study on Yiqi Fuzheng Prescription in anti⁃lung cancer metastasis by regulating the polarization of tumor associated macrophages
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 2, Pages: 67-74(2022)
- 作者机构：
  
  1.上海实验动物研究中心（上海 200032）
  2.上海中医药大学附属市中医医院肿瘤二科（上海 200071）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2104044
  CLC：
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刘怡辰,诸君,张国磊等.益气扶正方通过调控肿瘤相关巨噬细胞极化抗肺癌转移的实验研究[J].上海中医药杂志,2022,56(02):67-74.

LIU Yichen,ZHU Jun,ZHANG Guolei,et al.Experiment study on Yiqi Fuzheng Prescription in anti⁃lung cancer metastasis by regulating the polarization of tumor associated macrophages[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(02):67-74.
刘怡辰,诸君,张国磊等.益气扶正方通过调控肿瘤相关巨噬细胞极化抗肺癌转移的实验研究[J].上海中医药杂志,2022,56(02):67-74. DOI： 10.16305/j.1007-1334.2022.2104044.

LIU Yichen,ZHU Jun,ZHANG Guolei,et al.Experiment study on Yiqi Fuzheng Prescription in anti⁃lung cancer metastasis by regulating the polarization of tumor associated macrophages[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(02):67-74. DOI： 10.16305/j.1007-1334.2022.2104044.

摘要

目的,2,阐释益气扶正方调控肿瘤相关巨噬细胞表型转化的作用及机制。,方法,2,①建立体外诱导的M2型肿瘤相关巨噬细胞模型，采用CCK-8实验确定益气扶正方的给药浓度，流式技术鉴定给药后各组M1和M2型肿瘤相关巨噬细胞的表达情况，利用RT-PCR技术检测给药后各组肿瘤相关巨噬细胞中,CCL2,、,AMPK,、,mTOR ,mRNA表达水平，Western blot检测给药后各组肿瘤相关巨噬细胞中CCL2、AMPK、mTOR蛋白的表达水平。②建立Lewis肺癌小鼠皮下移植瘤模型，流式检测各组瘤体中M1和M2型肿瘤相关巨噬细胞的比例。,结果,2,①体外实验表明，益气扶正方能下调M2型TAMs标志物的表达，上调M1型TAMs标志物的表达；同时益气扶正方下调体外诱导的M2型肿瘤相关巨噬细胞中通路相关基因,CCL2,、,mTOR ,mRNA表达（,P<,0.001），上调,AMPK ,mRNA表达（,P<,0.05）；Western blot检测结果显示，与模型组比较，中药组CCL2、mTOR蛋白表达下调， AMPK表达上调（,P<,0.001）。②动物实验显示，益气扶正方可以抑制Lewis肺癌小鼠移植瘤的生长，瘤体细胞的流式检测结果显示，益气扶正方能抑制肿瘤组织中M2型肿瘤相关巨噬细胞表达，上调M1型肿瘤相关巨噬细胞表达，差异有统计学意义（,P<,0.05）。,结论,2,益气扶正方能抑制TAMs向M2型转化，其对TAMs极化的重要信号通路CCL2/AMPK/mTOR中各信号分子表达起着调控作用，说明该方可能通过调控信号通路CCL2/AMPK/mTOR，干预TAMs极化，从而发挥抑制肿瘤转移的作用。

Abstract

Objective,2,To elucidate the effect and mechanism of Yiqi Fuzheng Prescription in regulating the phenotypic transformation of tumor-associated macrophages （TAMs）.,Methods,2,①The model of M2 TAMs was established in vitro. The concentration of Yiqi Fuzheng Prescription was determined by CCK-8 experiment. The expression of M1 and M2 TAMs was identified by flow cytometry. The mRNA expression levels of CCL2， AMPK and mTOR were detected by RT-PCR， and Western blot was used to detect the expression of CCL2， AMPK and mTOR in TAMs. ②The subcutaneous transplanted tumor model of Lewis lung cancer in mice was established， and the proportion of M1 and M2 TAMs in each group was detected by flow cytometry.,Results,2,① Yiqi Fuzheng Prescription could down regulate the expression of M2 TAMs and up regulate the expression of M1 type TAMs in vitro； At the same time， Yiqi Fuzheng Decoction down regulated the mRNA expression of CCL2 and mTOR in M2 TAMs （,P<,0.001）， and up regulated the mRNA expression of AMPK （,P<,0.05）； Western blot showed that compared with the model group， the expressions of CCL2 and mTOR were down regulated and the expression of AMPK was up-regulated in the TCM group （,P<,0.001）. ②Animal experiments showed that Yiqi Fuzheng Prescription could inhibit the growth of Lewis lung cancer transplanted tumor in mice. The flow cytometry results of tumor cells showed that Yiqi Fuzheng Prescription could inhibit the expression of M2 TAMs， up regulate the expression of M1 TAMs in tumor tissues， and the difference was statistically significant （,P<,0.05）.,Conclusion,2,Yiqi Fuzheng Prescription can inhibit the transformation of TAMs into the M2 phenotype， and it plays a role in regulating the expression of each signaling molecule in CCL2/AMPK/mTOR， an important signaling pathway of TAMs polarization， suggesting that Yiqi Fuzheng Prescription may intervene in the TAMs polarizationto inhibit tumor metastasis through regulating the signaling pathway CCL2/AMPK/mTOR.

关键词

益气扶正方肿瘤相关巨噬细胞肺癌模型小鼠中药研究

Keywords

Yiqi Fuzheng Prescriptiontumor-associated macrophageslung cancermodel mousetraditional Chinese herbal medicine research

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