In vitro assays suggest Shenqi Fuzheng Injection has the potential to alter melanoma immune microenvironment
In vitro assays suggest Shenqi Fuzheng Injection has the potential to alter melanoma immune microenvironment
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DOI：
10.1016/j.jep.2016.08.038
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发表时间：
2016-12-24
影响因子：
5.4
通讯作者：
Yu, Zhi-Ling
中科院分区：
文献类型：
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作者：
Du, Juan;Cheng, Brian Chi Yan;Yu, Zhi-Ling
民族药理学相关性：参芪扶正注射液（SFI）是一种现代药物，由党参和黄芪制备，已被广泛用于包括黑色素瘤在内的癌症的辅助治疗。该制剂源自《国家中药处方集》中记载的一种配方。长期以来，该配方一直被用作治疗气虚的药物，气虚与癌症相关的疲劳和生活质量差密切相关。然而，SFI的抗黑色素瘤机制尚不清楚。在这里，我们通过体外实验重新编程肿瘤免疫微环境来测试SFI是否发挥抗黑素瘤作用。材料和方法：在SFI存在或不存在的情况下，测定Jurkat T细胞与A375细胞共培养时的细胞毒活性。用transwell实验系统检测Jurkat T细胞的迁移活性。采用real-time PCR和ELISA分别检测SFI存在或不存在时A375细胞中IL-10、TGF β和VEGF的mRNA表达和细胞因子的产生。结果：A375细胞与Jurkat T细胞在SFI （220 μ g/mL）存在下共培养，对A375细胞有明显的细胞毒作用。用SFI（110和220 μ g/mL）处理A375细胞的上清液，在transwell实验中显著增加Jurkat T细胞的迁移能力。SFI还显著降低A375细胞mRNA表达水平和免疫抑制因子IL-10、tgf - β和VEGF的释放，且呈浓度依赖性。结论：SFI增强Jurkat T细胞对A375黑色素瘤细胞的细胞毒性和迁移活性。这种作用与SFI抑制免疫抑制细胞因子的释放和A375黑色素瘤细胞的基因表达有关。这些体外研究结果表明，SFI可能在体内重新编程免疫抑制黑色素瘤微环境，以增强肿瘤浸润免疫细胞的细胞毒性。本研究为SFI在黑色素瘤治疗中的辅助应用提供了药理学基础。2016爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: A modern agent Shenqi Fuzheng Injection (SFI), prepared from Codonopsis Radix and Astragali Radix, has been commonly used as a supplementary therapy for cancers including melanoma. This agent was derived from a formula documented in the "National Collection of Chinese Medicine Prescriptions". The formula has long been used as a remedy for Qi deficiency that is closely associated with cancer-related fatigue and poor quality of life. However, the antimelanoma mechanisms of SFI remain unclear. Here we tested if SFI exerted antimelanoma effects by reprograming the tumour immune microenvironment using in vitro assays.Materials and methods: The cytotoxic activities of Jurkat T cells when co-cultured with A375 cells were determined in the presence or absence of SFI. The migratory activities of Jurkat T cells were examined in the transwell assay system. The mRNA expression and production of cytokines (IL-10, TGF beta and VEGF) in A375 cells in the presence or absence of SFI were determined by real-time PCR and ELISA, respectively.Results: When A375 cells were co-cultured with Jurkat T cells in the presence of SFI (220 mu g/mL), a potent cytotoxicity effect against A375 cells was observed. Supernatants from A375 cells that were treated with SFI (110 and 220 mu g/mL) significantly increased the migratory capacity of Jurkat T cells in transwell assays. SFI also markedly reduced the mRNA expression levels and the release of immunosuppressive cytokines IL-10, TGF-beta and VEGF in A375 cells in a concentration-dependent manner.Conclusions: SFI enhanced the cytotoxic and migratory activities of Jurkat T cells towards A375 melanoma cells. The effects were associated with SFI's suppression on immunosuppressive cytokines for their release from and gene expressions in A375 melanoma cells. These in vitro findings suggested that SFI might reprogramme the immunosuppressive melanoma microenvironment in vivo to enhance the cytotoxicity of tumour-infiltrating immune cells. This study provides a pharmacological basis for the adjunctive use of SFI in melanoma treatment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.