山奈酚抑制人類視網膜色素上皮細胞遷移之機制探討

Study of the inhibitory effects and it's underlying mechanisms of kaempferol on the cell migration of human retinal pigment epithelial cells

簡湘文(Hsiang-Wen Chien)

指導教授 ： 楊順發

中山醫學大學/醫學院/醫學研究所/博士(2020年)

https://doi.org/10.6834/csmu202000075

摘要

山奈酚 (Kaempferol)被報導是一種在不同的細胞株中具有抗發炎和抗遷移活性的類黃酮。然而，山奈酚對作用在人類視網膜色素上皮細胞 (ARPE-19)的效應及其潛在機制仍不清楚。在本研究中，我們證明了山奈酚以不具毒性的劑量抑制人類視網膜色素上皮細胞的遷移。我們發現山奈酚透過增加細胞外信號調節激酶1/2 (Extracellular signal-regulated kinase 1/2; ERK1/2)訊息傳遞的磷酸化表現，明顯降低了基質金屬蛋白酶-2 (Matrix metalloproteinase 2; MMP-2)的酵素活性和蛋白質表現。此外，ERK1/2專一性抑制劑PD98059可以顯著逆轉山奈酚對人類視網膜色素上皮細胞中細胞遷移和MMP-2酵素活性的抑制作用。我們的研究結果首次證明山奈酚能夠透過人類視網膜色素上皮細胞中的ERK1/2訊息傳遞路徑來抑制細胞遷移。

關鍵字

細胞外信號調節激酶1/2(ERK1/2)訊息傳遞 ； 山奈酚 ； 遷移 ； 基質金屬蛋白酶2

並列摘要

Kaempferol is a flavonoid with anti-inflammatory and anti-metastasis activity in different cell lines. However, the underlying mechanisms by which kaempferol acts on human retinal pigment epithelial (ARPE-19) cells remain unclear. In this study, we demonstrated that kaempferol inhibited migration and invasion in ARPE-19 cells at non-toxic concentractions. We discovered that kaempferol obviously reduced the enzyme activity and protein expression of matrix metalloproteinase-2 by increasing the phosphorylated levels of extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways. Additionally, ERK1/2-specific inhibitor PD98059 significantly reversed kaempferol’s inhibitory effects on migration and expression of MMP-2 in ARPE-19 cells. Overall, our results are the first to demonstrate that kaempferol is capable of inhibiting cell migration by targeting ERK1/2 signaling in human retinal pigment epithelial cells.

並列關鍵字

ERK1/2 signaling ； kaempferol ； migration ； MMP-2

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