Department of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, China.
Curr Drug Deliv. 2012 Jul;9(4):414-20. doi: 10.2174/156720112801323107.
To investigate the effect of LBP on differentiation and maturation of healthy human peripheral blood-derived dendritic cells cultured in different tumor microenvironment in vitro, and discuss the molecular and immunological mechanisms of LBP in treatment of tumor.
In this study, we procured the peripheral blood-derived dendritic cells precursor cell by the Density gradient centrifugation method, and used the tumor-cell supernatant to prepare conditioned medium. The GM-CSF and IL-4 induced DCs precursor cell differentiation to DCs, the TNF-α promoted the immature DCs developed to mature DCs. In this way, we detected the influence of LBP on the expressions of surface molecules of DCs cultured in different environments, and especially on the role of related-immunity and NF-κB activity.
In LBP-treated group, the molecular phenotype of DCs, its capacity to stimulate allogeneic lymphocyte proliferation, and the levels of IL-12p70 and IFN-γ secretion were higher than the untreated group (p < 0.05), with statistical significance. Meanwhile the expression of NF-κB of the DCs in the medium treated by the LBP was higher than the untreated group (p < 0.05), also with statistical significance. Between the two different tumor microenvironment groups, the cell nucleus protein NF-κB expression is obviously different, the hepG2.2.15 group higher than the hepG2 group.
LBP could increase the expression of the phenotype of DCs, the secretion of IL-12p70 and IFN-γ in MLR, and enhance the NF-κB expression, especially in the virus-related group, suggesting LBP plays the anti-tumor role stronger in the virus-related environment and this phenomenon correlates with the NF-κB signaling pathway.
研究 LBP 在体外不同肿瘤微环境中对健康人外周血来源树突状细胞(DC)分化成熟的影响,并探讨 LBP 治疗肿瘤的分子及免疫学机制。
本研究采用密度梯度离心法获取外周血来源的 DC 前体细胞,用肿瘤细胞上清液制备条件培养基。GM-CSF 和 IL-4 诱导 DC 前体细胞分化为 DC,TNF-α 促进未成熟 DC 发育为成熟 DC。以此检测 LBP 对不同环境中培养的 DC 表面分子表达的影响,特别是对相关免疫和 NF-κB 活性的作用。
在 LBP 处理组中,DC 的分子表型、刺激同种异体淋巴细胞增殖的能力以及 IL-12p70 和 IFN-γ 分泌水平均高于未处理组(p<0.05),差异有统计学意义。同时,LBP 处理的培养基中 DC 的 NF-κB 表达也高于未处理组(p<0.05),差异有统计学意义。在两种不同的肿瘤微环境组中,细胞核蛋白 NF-κB 的表达明显不同,hepG2.2.15 组高于 hepG2 组。
LBP 可增加 DC 表型的表达、MLR 中 IL-12p70 和 IFN-γ 的分泌,并增强 NF-κB 的表达,特别是在病毒相关组中,提示 LBP 在病毒相关环境中发挥更强的抗肿瘤作用,这一现象与 NF-κB 信号通路相关。