探討根皮素在人類子宮頸癌細胞轉移的抑制效果

Research of the inhibitory effect of phloretin on the metastasis of human cervical cancer cells

陳劭斌(Shao-Pin Chen)

指導教授 ： 陳霈霓

中山醫學大學/醫學院/醫學研究所 (原生化微生物免疫研究所)/碩士(2021年)

https://doi.org/10.6834/csmu202100138

摘要

癌症病人的死亡原因超過90%是由於癌細胞轉移所產生的疾病，而不是原發性腫瘤所引起，因此瞭解轉移的機轉對於癌症治療是非常重要的課題。轉移是一個很複雜的過程，其機制尚未完全明瞭，癌症病人原位腫瘤發生轉移的時間可能長達幾年甚至幾十年的時間，使得病人在治療的過程上變得更加複雜，存活率相對也下降許多。因此以針對預防癌症轉移的發生可以用來當做治療癌症的其中一種策略。根皮素是許多蔬菜、水果(包括蘋果和草莓)的果皮和根部中的活性成分，並具有許多藥理活性，例如抗氧化，抗發炎和抗癌作用。然而，根皮素對人類子宮頸癌的侵襲、遷移及轉移的影響仍不清楚。在本研究中，將人類子宮頸癌細胞株(SiHa細胞)以不同濃度(0~60 μM)的根皮素處理，再利用基質膠侵襲測定、明膠酶譜分析、細胞基質粘附測定、傷口癒合測定和西方墨點法，觀察根皮素對子宮頸癌細胞侵襲、遷移及上皮-間質細胞相互轉換機制的影響。結果顯示：根皮素(60 μM)能降低SiHa細胞中的基質金屬蛋白酶MMP-2、MMP-3和組織蛋白酶S的表現來抑制人類子宮頸癌細胞的侵襲和遷移，同時能降低間質細胞標誌物，如纖連蛋白，波形蛋白和Rho A的表現，並且能逆轉由轉化生長因子-β1所引發的上皮-間質細胞相互轉換。

關鍵字

根皮素 ； 轉移 ； 侵襲 ； 子宮頸癌

並列摘要

More than 90% of cancer-associated deaths being caused by metastatic disease rather than by the corresponding primary tumors. Therefore, understanding the mechanism of metastasis is a very important topic for cancer treatment. Metastasis is a very complicated process, and the mechanism is not fully understood. The time for cancer metastasize in situ may be several years to decades, which makes the treatment more complicated and the survival rate has decrecased a lot. Therefore, preventing cancer metastasis can be a strategie for cancer treatment. Phloretin is an active component in the peel and root skin of vegetables and fruits, including apples and strawberries, and has many pharmacological activities, such as antioxidant, anti-inflammatory, and anticancer effects. However, the phloretin's effect on human cervical cancer invasion, migration and metastasis remains unknown. In this study, the human cervical cancer cell lines (SiHa cells) were treated with different concentrations (0~60 μM) of phloretin, and the anti-invasive effect was evaluated using the Matrigel invasion assay, gelatin zymography assay, cell matrix adhesion assay, wound healing assay and western blotting. Phloretin (60 μM) showed marked suppression of invasion and migration through downregulation of matrix metalloproteinase (MMP)-2, MMP-3, and cathepsin S in human SiHa cervical cancer cells. Phloretin (60 μM) reversed the epithelial-mesenchymal transition induced by transforming growth factor-β1 and downregulated mesenchymal markers, such as fibronectin, vimentin, and RhoA.

並列關鍵字

phloretin ； metastasis ； invasion ； cervical cancer

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