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

Biomed Pharmacother. 2018 Jun:102:420-427. doi: 10.1016/j.biopha.2018.03.099. Epub 2018 Mar 22.

Abstract

The NF-κB/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-κB/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.

Keywords: Antitumor immunity; Hepatocellular carcinoma; NF-κB/IL-6/STAT3 axis; Natural herbal extract.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Humans
  • Immune System / drug effects
  • Immunity* / drug effects
  • Immunocompetence / drug effects
  • Interleukin-6 / metabolism*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Drugs, Chinese Herbal
  • Interleukin-6
  • NF-kappa B
  • NHE-06
  • STAT3 Transcription Factor