Sep 14th 2015, Beijing, China 

“A Novel Anti-cancer Agent Icaritin Suppresses Hepatocellular Carcinoma Initiation and Malignant Growth through the IL-6/JAK2/STAT3 Pathway” is published online on Oncotarget (Link: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=5578&author-preview=4ay). The study is completed by Prof. Jianqiang Cai’s lab in Cancer Hospital Chinese Academy of Medical Sciences (CHCAMS) and its collaborators. Dr. Hong Zhao from CHCAMS and Dr. Yuming Guo from Shenogen are co-first authors. 

Liver cancer is the fifth most common cancer and the third leading cause of cancer death worldwide. Hepatocellular Carcinoma (HCC) is the main type of liver cancer. China has a high incidence rate of HCC. More than 400 thousand patients are diagnosed as HCC in China every year, taking percentage of over a half of the global incidents. Due to multiple reasons including resistance and intolerance of chemo or radio therapies, HCC treatment has highly unmet medical needs. Tumor-initiating cells (TICs) are a subpopulation of cancer cells that have stem cell characteristics and are indispensable for tumorigenesis. Hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in HCC. The cytokine IL-6 plays a crucial role in immunology, inflammation and carcinogenesis. Recent studies show the IL-6/JAK2/Stat3 signaling pathway is involved in the maintenance and proliferation of HCICs. 

In this study Prof. Jianqiang Cai’s lab found for the first time that, icaritin, a prenylflavonoid derived from a traditional Chinese medicine Epimedium Genus, inhibited malignant growth of HCICs. Series of in vitro and in vivo experiments indicated that, icaritin reduced expression of IL-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Jak2 and Stat3, and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. In addition, compared to cytotoxic drug cisplatin, icaritin potently inhibited growth of HCC cells but has little toxicity in normal hepatocyte cells. The study provides a strong rational for development of icaritin as a novel therapeutic agent for effective and safe treatment of HCC by targeting HCICs. 

Icaritin is being investigated as a Class 1 TCM/Natural Medicine sponsored by Shenogen Pharma Group. Shenogen possesses robust intellectual property rights around icaritin and got supported from National “Twelfth Five-year Plan” Special Project for “Significant New Drug Development”. Shenogen is funded by top class VCs including IDG, Qiming and Legend Capital. Icaritin treatment in advanced HCC Ph II clinical trial is completing. Shenogen has submitted icaritin NDA as a breakthrough therapy to Beijing Food and Drug Administration. 

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 Genu, 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. 

About Shenogen

Shenogen Pharma Group is a drug discovery and development company based in Beijing, China, that dedicated the development of first-in-class therapeutics for cancer treatment. We possess robust intellectual property rights around a novel membrane-bound estrogen receptor, ER-alpha 36, which is related to tumor metastasis. Under the motto of “Better Medicine, Better Life” and a seasoned management team, together with our partners, Shenogen has developed an impressive product pipeline. Our pipeline consists of novel small molecule and antibody therapeutics for cancer treatment which includes liver cancer, breast cancer, other solid tumors and leukemia. Our lead molecule, icaritin, is completing Ph II clinical trial for treatment of advanced hepatocellular carcinoma.

(For more information, please visit www.shenogen.com.cn.)

2015年09月14日

Oncotarget: icaritin suppressing activity in HCC through IL-6/JAK2/STAT3 pathway

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