提取黄芪和黑酸莓对小胶质细胞和巨噬细胞的极化进行调节，抑制C6胶质母细胞瘤的生长和浸润。
Extract of Astragali Radix and Solanum nigrum Linne regulates microglia and macrophage polarization and inhibits the growth and infiltration of C6 glioblastoma.
发表日期：2023 Aug 22
作者：
Mingxue Shen, Suo Liu, Qin Wei, Xiong Zhang, Shiyu Wen, Runze Qiu, Yingbin Li, Hongwei Fan
来源：
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要：
胶质瘤相关巨噬细胞/巨噬细胞（GAMs）的极化影响了胶质瘤的生长和浸润。黄芪和龙葵是中药中传统的抗肿瘤组合，但其对胶质瘤的作用及机制尚不清楚。本研究探讨了黄芪和龙葵混合物（ARSN）对GAMs和胶质瘤细胞的体外和体内极化的影响，为胶质瘤治疗提供了新的思路。
采用UPLC-QTOF-MS方法检测了ARSN浸膏的质量。利用CCK-8法、胶萤法、划痕愈合法和流式细胞术研究了ARSN对C6细胞增殖、迁移和凋亡的影响。通过PCR、ELISA和流式细胞术验证了ARSN对GAMs极化的影响。此外，还建立了大鼠胶质瘤模型，评估了ARSN对胶质瘤生长、浸润和GAMs极化的影响。
体外实验结果表明，ARSN能有效抑制C6细胞的增殖和迁移，并促进凋亡。在大鼠原位肿瘤模型中，ARSN也能有效抑制肿瘤的生长和浸润。其中，龙葵部分具有较强的细胞毒性作用，而黄芪能够有效抑制GAMs的M2极化和肿瘤诱导的趋化因子产生，促进GAMs的M1表型，调节肿瘤免疫微环境以间接杀伤胶质瘤。
ARSN能够体内外抑制胶质瘤的生长。龙葵作用通过直接细胞毒性，而黄芪通过调节GAMs极化发挥作用。ARSN浸膏可作为胶质瘤治疗的潜在药物。
Copyright © 2023. Published by Elsevier B.V.
The polarization of glioma-associated microglia/macrophages (GAMs) affects the growth and infiltration of glioma. Astragali Radix (AR) and Solanum nigrum L. (SN) are traditional antitumor combinations in Chinese herbal medicine, but their roles and mechanisms against glioma are not yet clear.The effects of AR and SN compound (ARSN) on the polarization of GAMs and glioma cells in vitro and in vivo were studied, providing new ideas for the treatment of glioma.The UPLC-QTOF-MS method was used to examine the quality of ARSN extracts. The effects of ARSN on proliferation, migration and apoptosis of C6 cells were investigated using CCK-8 assay, colony-forming assay, wound healing assay and flow cytometry. The impact of ARSN on the polarization of GAMs was verified by PCR, ELISA, and flow cytometry. In addition, a rat glioma model was established to assess the effects of ARSN on glioma growth, infiltration, and polarization of GAMs.In vitro experiments, ARSN can effectively inhibit the proliferation and migration of C6 cells and promote apoptosis. In the rat orthotopic tumor model, ARSN also effectively inhibited tumor growth and infiltration. The SN part of ARSN has strong cytotoxicity. Meanwhile the AR part can effectively inhibit the M2 polarization of GAMs and chemokine production induced by tumor, promote the M1 phenotype of GAMs, and regulate the tumor immune microenvironment to indirectly kill glioma.ARSN inhibited glioma growth both in vitro and in vivo. SN takes effect through direct cytotoxicity, while AR works by regulating GAMs polarization. ARSN extracts can be used as a potential agent for glioma treatment.Copyright © 2023. Published by Elsevier B.V.