The anti-inflammatory NHE-06 restores antitumor immunity by targeting NF-κB/IL-6/STAT3 signaling in hepatocellular carcinoma
The anti-inflammatory NHE-06 restores antitumor immunity by targeting NF-κB/IL-6/STAT3 signaling in hepatocellular carcinoma
复制标题
抗炎 NHE-06 通过靶向肝细胞癌中的 NF-kappa B/IL-6/STAT3 信号恢复抗肿瘤免疫力
DOI：
10.1016/j.biopha.2018.03.099
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发表时间：
2018-06-01
影响因子：
7.5
通讯作者：
Wei, Jiwu
中科院分区：
文献类型：
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作者：
Lu, Xian;Wo, Guanqun;Wei, Jiwu
NF-kappa B/IL-6/STAT3炎症轴在多种炎症相关癌症中高度激活，并有助于抑制抗肿瘤免疫。本研究以无花果、蒲公英、当归、金银花、三七和银杏叶6种天然草本植物为原料，经水煎制出一种新型中药配方NHE-06。我们研究了NHE-06的抗炎特性及其对肝细胞癌（一种典型的炎症相关肿瘤）的抗肿瘤作用。我们发现NHE-06有效抑制NF-kappa B/IL-6/STAT3信号通路，增强体外和hcc小鼠的抗肿瘤免疫。在小鼠皮下肝癌模型中，我们发现NHE-06具有预防和治疗双重功能。此外，NHE-06的抗肿瘤作用不是细胞毒性作用，而是完整免疫不可或缺的，因为治疗效果仅在免疫功能正常的小鼠中实现，而在免疫功能低下的小鼠中无效。综上所述，抗炎NHE-06的新配方有效地恢复抗肿瘤免疫监视，可用于预防和/或治疗炎症相关癌症。
The NF-kappa B/IL-6/STAT3 inflammatory axis is highly activated in a variety of inflammation-related cancers and contributes to suppression of antitumor immunity. In this study, we generated a novel herbal formula NHE-06, a water-decocting extract from six natural herbals, Ficus carica, Taraxacum mongolicum, Angelica sinensis, Lonicera japonica, Pseudo-ginseng and Folium ginkgo. We investigated the anti-inflammatory properties of NHE-06 and its antitumor efficacy in hepatocellular carcinoma, a typical inflammation-related cancer. We found that NHE-06 effectively suppressed NF-kappa B/IL-6/STAT3 signaling and enhanced antitumor immunity both in vitro and in HCC-bearing mice. In a subcutaneous HCC mouse model, we found that NHE-06 possessed both preventive and therapeutic functions. Moreover, rather than the cytotoxic effects, the antitumor efficacy of NHE-06 was indispensable of intact immunity, since the therapeutic effect was only achieved in immunocompetent mice whereas failed in immunocompromised mice. Taken together, the novel formula of the anti-inflammatory NHE-06 effectively restores antitumor immunosurveillance and can be applied for prevention and/or treatment of inflammation-related cancers.