The anti-inflammatory NHE-06 restores antitumor immunity by targeting NF-κB/IL-6/STAT3 signaling in hepatocellular carcinoma

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.