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

• Published in: Integrative cancer therapies Vol. 16; no. 4; pp. 516 - 525
• Main Authors: Chuang, Meng-Hsien, Chang, Jinghua Tsai, Hsu, Li-Jin, Jan, Ming-Shiou, Lu, Fung-Jou
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.12.2017; SAGE Publishing
• Subjects: 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; Hep G2 Cells; HMGB Proteins - metabolism; 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; immunomodulation; Chinese medicine; splenocytes; coculture; Hepa 1-6; JC-001; hepatocellular carcinoma
• ISSN: 1534-7354; 1552-695X; 1552-695X
• DOI: 10.1177/1534735416664173

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.