植物半乳糖脂dLGG 藉由負調節TNF-α介導肺血管通透性與循環oxylipin的動態平衡來抑制黑色素瘤在小鼠體內的肺轉移
此研究首度證明從藥用植物昭和草分離出的半乳糖脂dLGG抑制黑素瘤肺轉移的新穎效果並闡明dLGG由維持肺臟組織緊密連接結構的正常通透性進而抑制黑素瘤細胞轉移至動物臟器的藥理活性和分子作用機制。此研究成果並為昭和草植物藥通過美國食品藥物管理局抗癌植物新藥的重要依據之ㄧ。我們研究結果証實dLGG和順鉑具有類似與顯著的抑制黑色素瘤(B16COX-2 / Luc)之癌肺轉移效果並延長小鼠的平均存活時間。小鼠餵食dLGG可顯著抑制轉移性黑色素瘤細胞的增殖和侵襲活性、負調節參與上皮-間質轉化的蛋白質的表現、抑制免疫查核點PD-1與 PD-L1的表達，並減少巨噬細胞、嗜中性白血球以及增加CD8+ T細胞滲入肺臟組織的微環境中。氧化脂質(oxylipins)在炎症和癌化過程扮演重要的角色。我們利用代謝體學研究發現dLGG顯著增加小鼠血清之oxylipin 17-HDHA，而我們更首度發現17-HDHA與 dLGG都可以抑制黑素瘤細胞分泌TNF-α進而抑制TNF-α所干擾之人類臍帶血管內皮細胞中緊密連接蛋白的表現量，並負調節Src/pyk2訊息傳導路徑藉以維持肺血管內皮細胞間功能與結構之完整性。同研究人員:楊仲智，張丞圭，張孟亭，徐麗芬*
徐麗芬
特聘研究員
(02) 2787-2102
jaclyn@gate.sinica.edu.tw
辦公室：農科大樓 A731
實驗室
位置: 農科大樓 A728
電話: (02) 2787-2100
- 07/2018- to date Distinguished Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica
- 05/2019-08/2019 Visiting Scholar of UC Davis, USA
- 03/2008- 8/2016 Vice Director, Agricultural Biotechnology Research Center, Academia Sinica
- 2008-2018 Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica
- 2008-2014 Coordinator of Molecular and Biological Agricultural Sciences program of
Taiwan International Graduate Program (TIGP-MBAS), Academia Sinica - 2003-2008 Associate Research Fellow, Agricultural Biotechnology Research Center, Academia Sinica
- 1998-2003 Assistant Research Fellow, Institute of BioAgricultural Sciences, Academia Sinica
- 1994-1997 Postdoctoral Research Fellow, Department of Biochemistry and Biophysics, Iowa State University, USA
- 1991-1992 Postdoctoral Research Fellow, Department of Agricultural Chemistry, National Taiwan University
- 1990-1991 Postdoctoral Research Fellow, Department of Biochemistry, Chang Gung University
SPECIAL ACHIEVEMENT
- Received US FDA approval for Zhaohe Cao (昭和草)-based botanical drug for an Investigational New Drug (IND) for cancer therapy (2017).