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中药JC-001在小鼠肝癌模型中的抗肿瘤活性通过免疫调节介导。

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

作者信息

Chuang Meng-Hsien, Chang Jinghua Tsai, Hsu Li-Jin, Jan Ming-Shiou, Lu Fung-Jou

机构信息

1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

2 Department of Chest Medicine, Chung Shan Medical University, Taichung, Taiwan.

出版信息

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 HO 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.

摘要

JC - 001是一种已被用于治疗肝脏疾病的中药;然而,其在癌症治疗中的意义尚未得到明确阐述。在本研究中,我们使用具有免疫活性的肿瘤模型来表征JC - 001的抗肿瘤活性。总共48只荷Hepa 1 - 6肿瘤的C57BL / 6小鼠被随机分为4组,并通过口服给予HO或JC - 001进行治疗。在肝癌细胞系,包括HepG2、Hep3B、SK - Hep - 1和Hepa 1 - 6,接受96小时的JC - 001治疗后,观察到较低的细胞毒性作用。相比之下,在相同的培养条件下,未观察到JC - 001对正常人肝细胞系THLE - 3有直接的细胞毒性作用。使用小鼠肿瘤模型,我们发现JC - 001可以抑制C57BL / 6小鼠的肿瘤生长,但对免疫缺陷小鼠无效。对C57BL / 6小鼠肿瘤的组织病理学分析显示,通过苏木精和伊红染色观察到,JC - 001治疗组的肿瘤中有免疫细胞浸润;此外,肿瘤中Ki67、缺氧诱导因子 - 1 - α和高迁移率族蛋白B1的表达水平受到抑制。共培养试验和小鼠脾脏mRNA定量PCR分析均表明,JC - 001可以抑制Th17免疫。我们的数据表明,JC - 001是一种细胞毒性较低的中药,可通过免疫调节显著抑制肿瘤生长。这种草药疗法在肝癌治疗的未来临床应用中具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/439e/5739137/1674a78985a7/10.1177_1534735416664173-fig1.jpg

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