Abstract
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.
Highlights
Human hepatocellular carcinoma (HCC) is the fifth most common cancer type and the third leading cause of cancer death worldwide [1]
We investigated the inhibitory function of Icaritin in the malignant growth of HCC and demonstrated that this inhibition activity functions through attenuating the Interleukin-6 Receptors (IL-6Rs)/Janusactivated kinases 2 (Jak2)/Signal transducer and activator of transcription 3 (Stat3) signaling pathway
Our results indicated that the Jak2/Stat3 pathway plays a critical role in hepatocellular carcinoma-initiating cells (HCICs)
Summary
Human hepatocellular carcinoma (HCC) is the fifth most common cancer type and the third leading cause of cancer death worldwide [1]. Similar incidence of HCC is observed in both developing and developed countries [2].Currently, surgical resection and transplantation still are main approaches to treat HCC while most of HCCs are inoperable due to advanced stages. After surgical resection, the long-term prognosis of HCC is still poor and recurrence remains a major problem [3]. Chemotherapeutics, such as Cisplatin and its relatives, are used to treat patients with advanced stage of HCC [4]. Chemoresistance and drug toxicity in www.impactjournals.com/oncotarget Cells injected DMSO. Cells survived from drugs treatment were subcutaneously injected with 5×105 and 5×104 respectively into each of NOD/SCID mice. Tumor incidence was analyzed after 40 days of cells injection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
