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http://dx.doi.org/10.5352/JLS.2011.21.11.1518

Drug Interaction between Ginseng Extract (GE) and Sorafenib  

Lee, Nam-Hee (Department of Pharmacology, Pusan National University School of Korean Medicine)
Park, Ho-Jae (Department of Pharmacology, Pusan National University School of Korean Medicine)
Rho, Ja-Sung (Department of Pharmacology, Pusan National University School of Korean Medicine)
Kim, Mi-Kyung (National Research and Development Center for Hepatobiliary Diseases, Pusan National University Yangsan Hospital)
Lee, Yu-Kyoung (National Research and Development Center for Hepatobiliary Diseases, Pusan National University Yangsan Hospital)
Cho, Eun-A (National Research and Development Center for Hepatobiliary Diseases, Pusan National University Yangsan Hospital)
Heo, Jeong (Department of Gastroenterology, Pusan National University Hospital)
Cho, Mong (Department of Gastroenterology, Pusan National University Yangsan Hospital)
Hwang, Tae-Ho (Department of Pharmacology, Pusan National University School of Korean Medicine)
Publication Information
Journal of Life Science / v.21, no.11, 2011 , pp. 1518-1525 More about this Journal
Abstract
Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.
Keywords
Sorafenib; pERK; Ginseng Extract; biomarker; drug interaction;
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