Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

被引:27
|
作者
Chou, Li-Fang [1 ]
Chen, Chi-Yuan [2 ,3 ,4 ]
Yang, Wan-Hua [5 ,6 ]
Chen, Chin-Chuan [2 ,7 ,9 ]
Chang, Junn-Liang [8 ]
Leu, Yann-Lii [7 ,10 ,11 ]
Liou, Miaw-Jene [12 ]
Wang, Tong-Hong [2 ,3 ,4 ,13 ]
机构
[1] Chang Gung Mem Hosp, Kidney Res Ctr, Taoyuan 33305, Taiwan
[2] Chang Gung Mem Hosp, Tissue Bank, Taoyuan 33305, Taiwan
[3] Chang Gung Univ Sci & Technol, Coll Human Ecol, Grad Inst Hlth Ind Technol, Taoyuan 33303, Taiwan
[4] Chang Gung Univ Sci & Technol, Coll Human Ecol, Res Ctr Ind Human Ecol, Taoyuan 33303, Taiwan
[5] Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Hsinchu Branch, Hsinchu 31064, Taiwan
[6] Yuanpei Univ Med Technol, Dept Med Lab Sci & Biotechnol, Hsinchu 30015, Taiwan
[7] Chang Gung Univ, Grad Inst Nat Prod, Taoyuan 33303, Taiwan
[8] Taoyuan Armed Forces Gen Hosp, Dept Pathol & Lab Med, Taoyuan 32551, Taiwan
[9] Ming Chuan Univ, Biomed Engn Dept, Taoyuan 33348, Taiwan
[10] Chang Gung Univ, Hlth Aging Res Ctr, Chinese Herbal Med Res Team, Taoyuan 33303, Taiwan
[11] Chang Gung Mem Hosp, Ctr Tradit Chinese Med, Taoyuan 33305, Taiwan
[12] Chang Gung Mem Hosp, Dept Internal Med, Div Endocrinol & Metab, Taoyuan 33305, Taiwan
[13] Chang Gung Mem Hosp, Dept Hepatogastroenterol, Liver Res Ctr, Taoyuan 33305, Taiwan
关键词
liver cancer; hydroxygenkwanin; epithelial-mesenchymal transition; FOXM1; miR-320a; MESENCHYMAL TRANSITION; HEPATITIS-B; CELLS; METASTASIS; THERAPIES; CURCUMIN; INVASION; DISEASE; TARGETS;
D O I
10.3390/biom10010020
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Daphne genkwa, a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid's cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor 'forkhead box protein M1' (FOXM1) and downstream FOXM1-regulated proteins related to epithelial-mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent.
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收藏
页数:15
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