期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 43, 期 5, 页码 1719-1729出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2013.2071
关键词
hepatocellular carcinoma; cancer stem cell; 8-bromo-7-methoxychrysin; Twist; epithelial-mesenchymal transition; beta-catenin
类别
资金
- National Natural Science Foundation of China [81172375]
- program for excellent talents in Hunan Normal University [ET13107]
- Construct Program of the Key Discipline of Basic Medicine in Hunan Province
- Research Fund for the Doctoral Program of Hunan Normal University [110656]
Emerging evidence has suggested that cancer stem cells with expression of surface biomarkers including CD133 and CD44 have more aggressive biological behavior, including epithelial-mesenchymal transition (EMT), which are closely related to invasion. The upregulation and nuclear relocation of the EMT regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). In this study, we aimed to isolate and characterize a small population of CD133(+) cells that existed in the HCC cell line SMMC-7721 by MACS and investigated the possible roles of 8-bromo-7-methoxychrysin (BrMC), a synthetic analogue of chrysin, in inhibiting the properties of CD133(+) sphere-forming cells (SFCs) derived from the HCC cell line SMMC-7721, namely liver cancer stem cells (LCSCs). Based on the data, BrMC inhibited the proliferation, self-renewal and invasion of LCSCs in vitro and in vivo, downregulated the expression of the LCSC biomarkers CD133 and CD44 and induced EMT by downregulating the expression of Twist and beta-catenin in LCSCs. BrMC potentiated the inhibition of LCSCs self-renewal after reduction of twist protein levels, which was attenuated when twist was overexpressed. This study not only provides an important experimental and theoretical basis for investigation of BrMC in LCSCs, but also helps in the development of effective therapeutic medicine for HCC.
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