Antitumor Activity of the Chinese Medicine JC-001 Is Mediated by Immunomodulation in a Murine Model of Hepatocellular Carcinoma

Integr Cancer Ther. 2017 Dec;16(4):516-525. doi: 10.1177/1534735416664173. Epub 2016 Oct 3.

Abstract

JC-001 is a Chinese medicine that has been used to treat liver disease; however, its significance in cancer treatment has not been characterized. In this study, we used an immunocompetent tumor model to characterize the antitumor activity of JC-001. A total of 48 Hepa 1-6 tumor-bearing C57BL/6 mice were randomly grouped into 4 groups and treated with H2O or JC-001 via oral administration. After hepatoma cell lines, including HepG2, Hep3B, SK-Hep-1, and Hepa 1-6, underwent 96 hours of JC-001 treatment, a low cytotoxic effect was observed. In contrast, no direct cytotoxic effect of JC-001 on a normal human liver cell line, THLE-3, was observed under the same incubation conditions. Using a murine tumor model, we found that tumor growth could be inhibited by JC-001 in C57BL/6 mice but not in immunodeficient mice. Histopathological analysis of tumors from C57BL/6 mice revealed immune cell infiltration in tumors from the JC-001-treated group, as observed by hematoxylin and eosin staining; in addition, Ki67, hypoxia-inducible factor-1-α, and high mobility group box 1 expression levels were suppressed in the tumors. Both the coculture assay and murine spleen mRNA quantitative PCR analyses demonstrated that JC-001 could suppress Th17 immunity. Our data suggest that JC-001 is a Chinese medicine with low cytotoxicity that can significantly suppress tumor growth by immune regulation. This herbal remedy has great potential for future clinical application in hepatoma therapy.

Keywords: Chinese medicine; Hepa 1-6; JC-001; coculture; hepatocellular carcinoma; immunomodulation; splenocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • HMGB Proteins / metabolism
  • Hep G2 Cells
  • Humans
  • Immunomodulation / drug effects
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • RNA, Messenger / metabolism

Substances

  • Antineoplastic Agents
  • Drugs, Chinese Herbal
  • HMGB Proteins
  • RNA, Messenger