Kim K H, Lee Y S, Jung I S, Park S Y, Chung H Y, Lee I R, Yun Y S
Laboratory of Immunology, Korea Cancer Center Hospital, Seoul, Korea.
Planta Med. 1998 Mar;64(2):110-5. doi: 10.1055/s-2006-957385.
We previously reported that an acidic polysaccharide from Panax ginseng named ginsan inhibits the incidence of benzo[a]pyrene-induced autochthonous lung tumors in mice. To elucidate the mechanism of antineoplastic activity, ginsan was tested for its ability to generate LAK cells and to produce cytokines. Spleen cells became cytotoxic to a wide range of tumor cells after 5 days of culture with ginsan in a non-major histocompatibility restricted manner and the activity of ginsan was 12 times higher than that of lentinan. The generation of killer cells by rIL-2 was neutralized only in the presence of anti-IL-2, whereas by ginsan it was neutralized in the presence of anti-IL-2 as well as anti-IFN gamma, or anti-IL-1 alpha. It was confirmed that ginsan induces the expression of mRNA for IL-2, IFN gamma, IL-1 alpha, and GM-CSF. Depletion of AsGM1+ cells from spleen cells reduced the generation of LAK by rIL-2. In contrast, depletion of AsGM1+ as well as Thy1+ cells, CD4+ cells, or DC8+ cells reduced the generation of LAK cells by ginsan. The serologic phenotype of rIL-2 induced LAK cells was CD8- cells, whereas the ginsan induced LAK cells, were CD8+ cells. Ginsan synergized with rIL-2 to generate LAK cells (2.0-15 fold) and the most dramatic synergy was seen at rIL-2 concentrations below 3 U/ml. Ginsan alone inhibited pulmonary metastasis of B16-F10 melanoma cells and enhanced the inhibition of lung colonies by rIL-2. These findings demonstrate that ginsan generates LAK cells from both NK and T cells through endogeneously produced multiple cytokines. This property may contribute to its effectiveness in the immunoprevention and immunotherapy of cancer.
我们之前报道过，一种来自人参的酸性多糖——人参聚糖，可抑制苯并[a]芘诱导的小鼠自发性肺肿瘤的发生。为阐明其抗肿瘤活性机制，对人参聚糖产生LAK细胞及产生细胞因子的能力进行了检测。脾细胞与人参聚糖培养5天后，以非主要组织相容性限制的方式对多种肿瘤细胞产生细胞毒性，且人参聚糖的活性比香菇多糖高12倍。rIL-2诱导的杀伤细胞生成仅在存在抗IL-2时被中和，而人参聚糖诱导的杀伤细胞生成在存在抗IL-2以及抗IFNγ或抗IL-1α时被中和。已证实人参聚糖可诱导IL-2、IFNγ、IL-1α和GM-CSF的mRNA表达。从脾细胞中去除AsGM1+细胞可降低rIL-2诱导的LAK细胞生成。相比之下，去除AsGM1+以及Thy1+细胞、CD4+细胞或DC8+细胞可降低人参聚糖诱导的LAK细胞生成。rIL-2诱导的LAK细胞的血清学表型为CD8-细胞，而人参聚糖诱导的LAK细胞为CD8+细胞。人参聚糖与rIL-2协同作用以生成LAK细胞（2.0至15倍），并且在rIL-2浓度低于3 U/ml时观察到最显著的协同作用。单独使用人参聚糖可抑制B16-F10黑色素瘤细胞的肺转移，并增强rIL-2对肺集落的抑制作用。这些发现表明，人参聚糖通过内源性产生的多种细胞因子从NK细胞和T细胞生成LAK细胞。这一特性可能有助于其在癌症免疫预防和免疫治疗中的有效性。
