期刊
ONCOTARGET
卷 6, 期 31, 页码 31927-31943出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5578
关键词
Icaritin; HCC; HCC initiating cells; IL-6 receptors; Stat3
资金
- China National Science and Technology Major Projects for Investigational New Drug [2012ZX09101215]
- National Natural Science Foundation of China [81201967, 31470073]
- Beijing Natural Science Foundation [7132193, 7144238]
- National High-tech R&D (863) Program of China [2015AA020408]
- capital health research and development of special [2014-1-4022]
- National Program on Key Basic Research Project of China (973 Program) [2014CBA02000]
- state key project on infection diseases of china [2012ZX10002016]
- Beijing Nova Programme [2009A69, 2013073]
Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM-positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3. Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC.
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