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人参和黄芪的水提物调节巨噬细胞极化,并协同增强 DDP 的抗癌作用。

Water extract of ginseng and astragalus regulates macrophage polarization and synergistically enhances DDP's anticancer effect.

机构信息

School of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

School of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.

出版信息

J Ethnopharmacol. 2019 Mar 25;232:11-20. doi: 10.1016/j.jep.2018.12.003. Epub 2018 Dec 5.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

In traditional Chinese medicine, supplementing Qi and strengthening body resistance are an important principle of anticancer treatment. Panax ginseng C.A.Mey. (ginseng) and Astragalus membranaceus Bunge (astragalus) are the representative herbs for this therapeutic principle.

AIM OF THE STUDY

This study aims to explore the effect of the water extract of ginseng and astragalus (WEGA) on regulating macrophage polarization and mediating anticancer in the tumor microenvironment.

MATERIALS AND METHODS

A549 cells were cultured in tumor-associated macrophage (TAM) supernatant with various concentrations of WEGA (0, 5, 10, 20 mg/mL). A549 cell proliferation was determined through methyl thiazole tetrazolium (MTT) assay and real-time cell analysis (RTCA), respectively. In vivo experiments were performed with a Lewis lung cancer (LLC) xenograft mouse model. Forty-eight mice were divided into six groups and treated with saline, WEGA, or cis-diamine dichloro platinum (DDP) with dosage of WEGA (0, 30, 60, 120 mg/kg body weight/day). The different groups were administered with drugs via oral or intraperitoneal injection once a day for 21 consecutive days. Tumor inhibition rate, spleen index, thymus index, cytokine, protein, and mRNA expression levels were detected in mice.

RESULTS

In a co-culture system, WEGA remarkably inhibited A549 cell proliferation, promoted the expression of M1 macrophage markers and inhibited M2 TAMs markers. Therefore, WEGA affected the biological behavior of cancer cells by regulating the expression of some markers relevant to macrophage polarization. In addition, the group of WEGA and DDP chemotherapy effectively inhibited the transplanted tumor growth in mice and improved weight loss and immunosuppressive with the cisplatin inducing.

CONCLUSIONS

This study provides mechanistic insights into the anticancer effect of WEGA through the regulation of macrophage polarization and highlights that WEGA could be a novel option for integrative cancer therapies.

摘要

民族药理学相关性

在中医中,补气扶正是抗癌治疗的一个重要原则。人参 Panax ginseng C.A.Mey.(人参)和黄芪 Astragalus membranaceus Bunge(黄芪)是这一治疗原则的代表性草药。

研究目的

本研究旨在探讨人参和黄芪水提物(WEGA)对调节肿瘤微环境中巨噬细胞极化和介导抗癌作用的影响。

材料和方法

用不同浓度的 WEGA(0、5、10、20mg/mL)培养 A549 细胞在肿瘤相关巨噬细胞(TAM)上清液中。通过噻唑蓝(MTT)法和实时细胞分析(RTCA)分别测定 A549 细胞的增殖。使用 Lewis 肺癌(LLC)异种移植小鼠模型进行体内实验。将 48 只小鼠分为六组,分别用生理盐水、WEGA 或顺铂(DDP)处理,WEGA 的剂量为 0、30、60、120mg/kg 体重/天。不同组每天通过口服或腹腔注射给予药物,连续 21 天。检测小鼠的肿瘤抑制率、脾指数、胸腺指数、细胞因子、蛋白和 mRNA 表达水平。

结果

在共培养体系中,WEGA 显著抑制 A549 细胞增殖,促进 M1 巨噬细胞标志物的表达,抑制 M2 TAMs 标志物的表达。因此,WEGA 通过调节与巨噬细胞极化相关的某些标志物的表达,影响癌细胞的生物学行为。此外,WEGA 和 DDP 化疗组有效地抑制了小鼠移植瘤的生长,并改善了顺铂诱导的体重减轻和免疫抑制。

结论

本研究通过调节巨噬细胞极化,为 WEGA 的抗癌作用提供了机制见解,并强调 WEGA 可能成为癌症综合治疗的一种新选择。

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