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白花蛇舌草多糖增强细胞因子诱导的杀伤细胞的抗肿瘤活性。

Polysaccharides from Hedyotis diffusa enhance the antitumor activities of cytokine-induced killer cells.

机构信息

Grade Three Laboratory of Traditional Chinese Medicine Preparation of National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, PR China.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China; Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou 510060, PR China.

出版信息

Biomed Pharmacother. 2019 Sep;117:109167. doi: 10.1016/j.biopha.2019.109167. Epub 2019 Jul 6.

Abstract

Hedyotis diffusa is a well-known traditional Chinese herbal medicine. The polysaccharides extracted from H. diffusa (HDP) exhibit a range of pharmacological activities. Transfusion of cytokine-induced killer (CIK) cell is one type of adoptive cellular immunotherapy, which is becoming an important method of cancer immunotherapy. In this present study, we investigate the immunostimulatory effect of HDP on CIK cells. CIK cells were generated by culturing and stimulating peripheral blood monocytes of healthy volunteers. They were treated with HDP at three different concentrations (10, 50, and 100 μg/mL). The effect of HDP on CIK cell populations, intracellular cytokine production, and apoptosis was examined by flow cytometry. The antitumor effect of HDP on CIK cells was determined by cytotoxicity assay. Furthermore, the effect of HDP on the antitumor activity of CIK cells in a mouse model was investigated. HDP increased the percentage of CD3CD56 CIK cells but did not significantly change the percentage of CD4, CD8, or CD4CD25 CIK cells. The HDP-treated CIK cells showed a greater ability to kill tumor cells, as well as higher production of interferon-γ and tumor necrosis factor-α, compared with the no-HDP-treated CIK cells. The HDP-treated CIK cells also found a lower apoptosis level in vitro. Moreover, HDP combined with CIK cells had a stronger inhibitory effect on tumor growth in the mouse model compared with the CIK or HDP treatment alone. In conclusion, the results indicated that HDP enhanced the antitumor activity of CIK cells and could be used for cancer immunotherapy combined with CIK cell therapy.

摘要

白花蛇舌草是一种广为人知的传统中药。从白花蛇舌草中提取的多糖(HDP)具有多种药理活性。细胞因子诱导的杀伤(CIK)细胞输注是一种过继性细胞免疫疗法,正在成为癌症免疫治疗的重要方法。在本研究中,我们研究了 HDP 对 CIK 细胞的免疫刺激作用。CIK 细胞通过培养和刺激健康志愿者的外周血单核细胞产生。用三种不同浓度(10、50 和 100μg/mL)的 HDP 处理 CIK 细胞。通过流式细胞术检测 HDP 对 CIK 细胞群体、细胞内细胞因子产生和凋亡的影响。通过细胞毒性测定法确定 HDP 对 CIK 细胞的抗肿瘤作用。此外,还研究了 HDP 对荷瘤小鼠模型中 CIK 细胞抗肿瘤活性的影响。HDP 增加了 CD3CD56 CIK 细胞的百分比,但对 CD4、CD8 或 CD4CD25 CIK 细胞的百分比没有显著影响。与未用 HDP 处理的 CIK 细胞相比,用 HDP 处理的 CIK 细胞具有更强的杀伤肿瘤细胞的能力,以及更高的干扰素-γ和肿瘤坏死因子-α的产生。用 HDP 处理的 CIK 细胞在体外也发现凋亡水平较低。此外,与 CIK 或 HDP 单独治疗相比,HDP 联合 CIK 细胞对荷瘤小鼠模型中的肿瘤生长具有更强的抑制作用。总之,结果表明 HDP 增强了 CIK 细胞的抗肿瘤活性,可与 CIK 细胞治疗联合用于癌症免疫治疗。

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