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Drug Interaction between Ginseng Extract (GE) and Sorafenib
이남희(Nam-Hee Lee),박호재(Ho-Jae Park),노자성(Ja-Sung Rho),김미경(Mi-Kyung Kim),이유경(Yu-Kyoung Lee),조은아(Euna Cho),허정(Jeong Heo),조몽(Mong Cho),황태호(Tae-Ho Hwang) 한국생명과학회 2011 생명과학회지 Vol.21 No.11
쏘라페닙은 간암 치료제로 승인된 유일한 약이다. 전세계 암환자들의 인삼추출물 사용이 증가 되고 있지만 쏘라페닙과의 상호작용에 대한 연구는 부족하다. 사람의 간암 세포주와 생쥐 모델을 사용하여 쏘라페닙과 인삼추출물의 약물 상호작용을 알아보고자 하였다. 저농도 인삼추출물 투여시 암세포주의 성장과 pERK(phosphorylation of extracellular signal-regulated kinase)의 증가가 관찰되었고 고농도 투여시 암세포 억제와 pERK 감소가 관찰되었다. 성장 사이클이 없는 세포에서 쏘라페닙의 항암 효과가 감소한 반면 저농도 인삼 투여시 항암 효능이 증진되어 나타났다. PD98059 (ERK 인산화 억제재)은 효과적으로 ERK 인산화를 억제하여 인삼추출물의 쏘라페닙 감작 작용을 억제시켰다. 생쥐 간암 세포주 모델에서, 저농도 인삼추출물은 다소 암세포 크기를 증가 시켰지만 고농도 투여시 감소시켰다. 그러나, 인삼추출물과 쏘라페닙 동시 투여시 항암 효능은 현저히 증가되었다. 정상조직에서 저농도 인삼에 의해 PERK 증가가 관찰되었으며 이것은 홍삼에 의한 독성 증가와 관련될 것으로 추정되었다. 결론적으로 인삼추출물과 쏘라페닙은 농도에 따라 항암효능을 증가 시킬 수 있음을 보여 주었지만 독성의 가능성도 함께 증가시켰다. 인삼추출물과 쏘라페닙 약물 상호작용에 대한 더 면밀한 연구가 필요할 것으로 보인다. 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.
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일본동양의학회지에 수록된 ‘부작용’에 관한 논문 분석 : 한약 단독 투여시의 부작용
강휘중(Hwi-Joong Kang),김효동(Hyo-Dong Kim),박호재(Ho-Jae Park),이부균(Boo-Kyun Lee),박성하(Seong-Ha Park),이장천(Jang-Cheon Lee) 한국한의학연구원 2011 한국한의학연구원논문집 Vol.17 No.2
Objective : This study reviews the articles about ‘Side effect’ published in the Japanese Journal of Oriental Medicine to better understand about side effects of herbal medication and to encourage clinicians, the authorities and the public to establish side effects reporting system. Method : We searched articles published in the Japanese Journal of Oriental Medicine by using keyword ‘副作用(Side effect)’ in the CiNii. Results : Among the 118 articles collected, 14 are clinical articles about side effect of prescriptions, 13 are reports about side effect of prescriptions presented from Japanese Ministry of Health, Labour and Welfare, 36 are clinical articles about relief of side effects derived from taking western medicine by taking a herbal prescription, 8 are studies about the effect of a herbal prescription combined with western medicine or comparative studies between a herbal prescription and western medicine, and so on. Conclusions : Lots of articles deal with side effects of Aconiti Lateralis Radix Preparata, Bupleuri Radix and so on. When side effects occurred, removing a certain herbal drug or quitting a herbal prescription is helpful to relieve or disappear the side effects. And Side effects reporting system should be established to guide safe medication use and treatment for patients. In order to establish side effects reporting system, the standardization of herbal drugs is needed.
ScienceON
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