柚皮素對於抑制肺癌以及骨肉瘤細胞轉移的分子機轉

The Molecular Mechanisms of Naringenin on the Inhibition of Migration of Lung Cancer and Osteosarcoma Cells

章育銘(Yuh-Ming Chang)

指導教授 ： 許立松

中山醫學大學/醫學院/生化微生物免疫研究所/博士(2020年)

https://doi.org/10.6834/CSMU202000012

摘要

非小細胞肺癌與惡性骨肉瘤有高死亡率，因為非常容易癌細胞早期轉移，對化學治療產生抗性。柚皮素 (naringenin)，是從好幾種水果萃取得到的生物活性化合物具有抗發炎和抗癌症作用，甚至可以減少好幾種癌細胞的轉移。然而，柚皮素對於抑制這兩種癌細胞轉移的作用仍不清楚。因此本實驗探討是否柚皮素抑制肺癌A549細胞與human osteosarcoma 143B細胞轉移的作用與機制。我們的結果顯示以0-300 μM濃度的柚皮素處理，並沒有顯著影響A549細胞與osteosarcoma 143B細胞的增生。然而柚皮素可以抑制A549細胞與 osteosarcoma 143B細胞之移行且與劑量是正相關的。 柚皮素可以減少A549細胞與osteosarcoma 143B細胞之matrix metalloproteinase (MMP)-2和-9活性，也是與劑量是正相關的。 且進一步觀察到柚皮素抑制A549細胞AKT活性，抑制osteosarcoma 143B細胞中Snail的表現。綜合本實驗結果，顯示柚皮素可以藉由抑制MMP，AKT活性和調控上皮間質轉化標記蛋白等機轉，來抑制肺癌細胞A549與 osteosarcoma 143B細胞的轉移。

關鍵字

柚皮素 ； 小細胞肺癌 ； 骨肉瘤 ； 第二型及第九型基質金屬蛋白酶

並列摘要

Non-small-cell lung cancer and osteosarcoma have high mortality rate due to their high metastatic potential and resistance to chemotherapy. Naringenin, a bioactive compound identified in several fruits, displays anti-inflammatory and anti-tumor effects. Furthermore, naringenin mitigates the migration of several human cancer cell types. However, the effects of naringenin on lung cancer and osteosarcoma remain unclear. The current study investigated the mechanisms of naringenin on the migration of lung cancer A549 and human osteosarcoma 143B cells. The results indicate that no overt alteration of cell viability in response to naringenin (0-300 μM) treatment in A549 cell and human osteosarcoma 143B cell. Inhibition of migration was found in A549 and osteosarcoma cells treated with naringenin in proportion to its concentration. In addition, naringenin exhibited a concentration-dependent inhibition of matrix metalloproteinase (MMP)-2 and -9 activities. Furthermore, naringenin also inhibited the activities of AKT in A549 cell and reduced the expression of mesenchymal marker Snail in osteosarcoma cells dose-dependently. These observations indicated that naringenin inhibited the migration of lung cancer A549 and osteosarcoma 143B cell through several mechanisms, including inhibition of MMPs, AKT activities and modulation of epithelial-mesenchymal transition markers.

並列關鍵字

Naringenin ； Non-small-cell lung cancer ； Osteosarcoma ； Matrix metalloproteinases-2/-9

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