探討甘草查爾酮A抗人類多形性膠質母細胞瘤轉移之機制

甘草查爾酮A (Licochalcone A, LicA)已被報告具有抗腫瘤的功能。然而在對人類膠質瘤細胞依然未知。這項研究中，我們觀察到甘草查爾酮A顯著抑制人類多形性膠質母細胞(M059K、U-251 MG和GBM8901)的細胞移動和侵犯能力，並且沒有細胞毒性。利用人類蛋白酶抗體排列(Human proteinase antibody array)及免疫墨點分析(immunoblot analysis) 顯示經甘草查爾酮A處理的人類多形性膠質母細胞之ADAM9 (A disintegrin and a metalloprotease 9)蛋白表現明顯被抑制。同時利用重組人類ADAM9 (Recombinant human ADAM-9, Rh-ADAM9)技術處理也足夠回復已被甘草查爾酮A抑制人類多形性膠質母細胞之ADAM9的表現、移動和侵犯能力。此外，甘草查爾酮A也會抑制人類多形性膠質母細胞的MEK/ERK的活化訊息途徑。甘草查爾酮A與PD98059 (MEK抑制劑)共同處理人類多形性膠質母細胞內ADAM9表現和細胞移動和侵犯具有共同抑制效果，本研究證實甘草查爾酮A抑制細胞移動和侵犯是經由MEK/ERK和ADAM9的訊息途徑。綜合以上結果，這是第一個研究證明甘草查爾酮A具有抗轉移能力來對抗人類多形性膠質母細胞瘤細胞。

Licochalcone A (LicA) has been reported to possess antitumor properties. However, its effect on human glioma cells remains unknown. In this study, we observed that LicA significantly inhibit cell migration and invasion activities of human glioma cells (M059K、U-251 MG and GBM8901) and exhibited no cell cytotoxicity. Human proteinase antibody array and immunoblot analysis indicated that the LicA treatment inhibited the expression of ADAM9 protein in human glioma cells. Recombinant human ADAM9 (Rh-ADAM9) treatment significantly reversed the LicA-induced reduction in the ADAM9 level and the cell migration and invasion activities of human glioma cells. Additionally, the phosphorylation/activation of the mitogen-activated protein kinase kinase (MEK)-extracellularly responsive kinases (ERK) signaling pathway was significantly suppressed in LicA-treated human glioma cells. Cotreatment with LicA and PD98059 (MEK inhibitor) synergistically inhibited ADAM9 expression, cell migration, and cell invasion, which suggested that the MEK-ERK signaling pathway was involved in LicA-induced inhibition of ADAM9 expression and invasion activity of human glioma cells. These findings are the first evidence of the LicA’s anti-invasive properties against human glioma cells.