槲皮素透過抑制NF-κB及基質金屬蛋白酶-2/-9訊息途徑來抑制人類口腔癌細胞(SAS)的轉移及侵襲

Quercetin Inhibits Migration and Invasion of SAS Human Oral Cancer Cells through Inhibition of NF-κB and Matrix Metalloproteinase-2/-9 Signaling Pathways

賴婉文(Wan-Wen Lai)

指導教授 ： 蔡崇弘

中山醫學大學/醫學院/醫學研究所/博士(2013年)

摘要

研究目的：槲皮素是一個存在於洋蔥中的主要的類黃酮化合物，已有研究指出具有廣泛的藥理性質，其中包括抗癌活性。我們先前研究發現，槲皮素會誘導人類口腔癌細胞SAS細胞的細胞毒殺作用。
研究方法與結果：在本研究中，我們發現SAS細胞在24小時以槲皮素培養處理時，槲皮素具顯著性地會降低SAS細胞的修復及增生。結果發現，利用西方墨點法及明膠蛋白酵素電泳技術證實槲皮素對SAS細胞能抑制基質金屬蛋白酶（MMP）-2和-9的表現及活性。另也利用西方墨點法測定發現槲皮素亦降低MMP-2, -7, -9 ,-10, VEGF, NF-κB (P65), iNOS COX-2, uPA, PI3K, IKBα, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3, MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN和p-c-JUN的蛋白表現，但槲皮素對RhoA,PKC和RAS並沒有影響。利用共軛焦顯微鏡觀察發現槲皮素處理SAS細胞時會促進RhoA和ROCK-1的表現，但對NF-κB(p65)會抑制其表現。
結論：綜上所述，槲皮素能抑制SAS細胞的轉移和侵襲能力是透過RAS及RhoA的down-regulation，而阻斷MAPK、PI3K/AKT路徑、NF-κB與uPA，其導致使MMP-2和MMP-9受到抑制。

關鍵字

槲皮素 ； 轉移 ； 侵襲 ； 基質金屬蛋白酶-2,-9 ； NF-κB ； 人類口腔癌細胞(SAS)

並列摘要

Objective：Quercetin, a principal flavanoid compound and exist in onions, has been shown to possess a wide spectrum of pharmacological properties, including anticancer activities. Our earlier study has shown that quercetin induced cytotoxic effects on human oral cancer SAS cells.
Methods and Results: In this study, we found that quercetin significantly reduced wound closed of SAS cells in culture plates after 24h treatments. Results indicated that quercetin inhibited the expressions and activities of metalloproteinase (MMP)-2 and MMP-9 that were measured by Western blotting and gelatin zymography. The results from Western blotting also showed that quercetin decreased the protein levels of MMP-2, -7, -9 and -10, VEGF, NF-κB (p65), iNOS, COX-2, uPA, PI3K, IKBα, IKB-α/β, p-IKKα/β, FAK, SOS1, GRB2, MEKK3, MEKK7, ERK1/2, p-ERK1/2, JNK1/2, p38, p-p38, c-JUN and p-c-JUN but it did not affect RhoA, PKC and RAS in SAS cells. Confocal laser microscope system also showed that quercetin promoted the expressions of RhoA and ROCK-1 but inhibited the expression of NF-κB p65 in SAS cells.
Conclusion: Taken together, it is concluded that inhibition of migration and invasion of SAS cells by quercetin is associated with the down-regulation of RAS, RhoA, blocking MAPK and PI3K/AKT signaling pathways and NF-κB and uPA, resulting in inhibition of MMP-2 and MMP-9 signaling.

並列關鍵字

Quercetin ； migration ； invasion ； MMP-2 ； MMP-9 ； NF-κB ； SAS human oral cancer cells

參考文獻

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