Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice

BMC Complementary and Alternative Medicine

Research Article

Chien-Yun Hsiang¹  Shun-Ting Chou²  Su-Yin Chiang²  Hsin-Yi Lo²  Tin-Yun Ho³  Ching-Liang Hsieh⁴  Ming-Tsung Lai⁵  Hui-Fen Huang⁶ 

[1] Department of Microbiology, China Medical University, 40402, Taichung, Taiwan;Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, 40402, Taichung, Taiwan;Graduate Institute of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, 40402, Taichung, Taiwan;Department of Health and Nutrition Biotechnology, Asia University, 41354, Taichung, Taiwan;Graduate Institute of Integrated Medicine, China Medical University, 40402, Taichung, Taiwan;Department of Chinese Medicine, China Medical University Hospital, 40447, Taichung, Taiwan;School of Medicine, Chung-Shan Medical University, 40201, Taichung, Taiwan;Department of Pathology, Chung-Shan Medical University Hospital, 40201, Taichung, Taiwan;School of Post-baccalaureate Chinese Medicine, Tzu Chi University, 97004, Hualien, Taiwan;

关键词: Zuo-Jin-Wan;    Anti-cancer;    Coptis chinensis;    Evodia rutaecarpa;    Xenograft mouse model;   

DOI  :  10.1186/s12906-017-1586-6

 received in 2016-10-05, accepted in 2017-01-14,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundZuo-Jin-Wan (ZJW), a two-herb formula consisting of Coptis chinensis (CC) and Evodia rutaecarpa (ER), is commonly used in traditional Chinese medicine for the treatment of cancers. However, the efficacies and mechanisms of ZJW and its alkaloid components on cancers are still unclear.MethodsHere we investigated the anti-cancer effects and mechanisms of ZJW, CC, ER, berberine, and evodiamine in cells and in intrahepatic xenograft mice.ResultsTreatment of HepG2 cells with ZJW, CC, ER, berberine, and evodiamine significantly displayed cytotoxic effects in a dose- and time-dependent manner. Hierarchical cluster analysis of gene expression profiles showed that CC and ZJW shared a similar mechanism for the cytotoxic effects, suggesting that CC was the active ingredient of ZJW for anti-cancer activity. Network analysis further showed that c-myc was the likely key molecule involved in the regulation of ZJW-affected gene expression. A human hepatoma xenograft model was established by intrahepatic injection of HepG2 cells containing nuclear factor-κB-driven luciferase genes in immunocompetent mice. In vivo bioluminescence imaging showed that cells had been successfully transplanted in mouse liver. Oral administration of ZJW for 28 consecutive days led to a significant decrease in the accumulation of ascites, the ratio of tumor-to-liver, and the number of transplanted cells in livers.ConclusionsIn conclusion, our findings suggested for the first time that ZJW significantly suppressed human cancer cell growth in orthotopic HepG2 xenograft-bearing immunocompetent mice. Moreover, c-myc might play a potent role in the cytotoxic mechanisms of ZJW, CC, ER, berberine, and evodiamine.

【 授权许可】

CC BY   
© The Author(s). 2017