柚皮素藉由逆轉上皮細胞間質轉化作用進而抑制前列腺癌細胞之轉移

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 博碩士論文 > Item 310902500/8996

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Title:	柚皮素藉由逆轉上皮細胞間質轉化作用進而抑制前列腺癌細胞之轉移 Naringenin Reverse Epithelial-Mesenchymal Transition and Suppress Prostate Cancer Cells Metastasis
Authors:	洪銘謙 Hong, Ming-Chian
Contributors:	中山醫學大學：生化暨生物科技研究所;許立松
Keywords:	柚皮素;上皮細胞間質轉化作用;前列腺癌 Naringenin;Epithelial-Mesenchymal Transition;Prostate Cancer
Date:	2013
Issue Date:	2014-01-15T04:43:23Z (UTC)
Abstract:	前列腺癌已成為美國男性最常見的癌症之一，其發生率僅次於皮膚癌，且位居男性癌症死亡率第二位。在台灣，近年來男性罹患前列腺癌的發生率及死亡率有逐年增高的趨勢。癌症所造成的高死亡率，大部分都與其轉移相關。因此，對於癌症轉移的治療及預後之相關研究探討，是刻不容緩的。越來越多的證據顯示，上皮細胞間質轉化作用（EMT）是與癌病變及癌細胞的移動和侵襲能力息息相關的。近期的研究結果指出，各種不同的中草藥具有不同的抗癌特性，包括抑制癌細胞的增生及誘導細胞凋亡作用。柚皮素廣泛存在於柑橘類水果，其被證實具有抗氧化、抗發炎、降血指、清除自由基、促進新陳代謝及免疫功能的調節等功能。然而，柚皮素對於上皮細胞間質轉化作用的相關研究目前為止仍是相當限的。故本研究加以探討柚皮素是否能藉由反轉上皮細胞間質轉化作用作用，進而抑制人類前列腺癌細胞的移動及侵襲能力。本篇研究以MTT assay來檢測柚皮素對前列腺癌細胞DU145與PC3的生長影響，利用傷口癒合作用（wound healing assay）與Boyden chamber assay檢測，發現柚皮素具有抑制前列腺癌細胞PC3的移動和侵襲能力。此外，前列腺癌細胞PC3經柚皮素處理後，上皮細胞的特徵E-cadherin蛋白表現量會增加，而間質細胞的特徵Vimentin與相關轉錄因子Snail、Slug及Twist皆會隨著藥物濃度的提高而降低蛋白表現，進而抑制其移動和侵襲能力。綜合以上結果，柚皮素可能是透過抑制轉錄因子的活性，達到反轉上皮細胞間質轉化作用之作用，進而抑制前列腺癌細胞的增生及轉移能力。 Prostate cancer is the most common cancer excluding skin cancer and the second leading of cancer-related deaths among men in United States. It is well recognized that the majority of cancer related deaths is caused by metastasis. Therefore, there is an urgent issue for the development of therapeutic intervention specifically targeted to the metastatic process. Growing evidence indicate that epithelial-mesenchymal transitions (EMT) is associated with carcinogenesis, cancer motility and invasion. Recently, Chinese medicinal herbs have been reported to have various anti-carcinogenesis properties, including inducing cell apoptosis and suppressing cell proliferation. Naringenin (Nar), which is plentiful in citrus fruits, has been shown to exhibit anti-inflammatory, anti-oxidant and hypolipidemic effects. However, limited studies are available concerning the potential of Nar in reversing EMT. Thus, we want to investigate whether Nar might suppress cancer motility and invasion via reverse EMT of prostate cancer cells. In our study, treatment with Nar caused reducing of DU145 and PC3 cells proliferation by MTT assay. Via wound healing assay and Boyden chamber assay, we found that Nar can suppress PC3 cells migration and invasion. Furthermore, we found Nar increased the expression of the epithelial phenotype marker, E-cadherin, and repressed the level of the mesenchymal phenotype markers such as Vimentin in proportion to concentration. Nar also inhibited EMT-inducing transcription factors including Snail, Slug and Twist, which reduce cell motility and invasion. Finally, it was concluded that Nar inhibited proliferation and suppressed prostate cancer cell metastasis in vitro by reversing EMT progression.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/8996
Appears in Collections:	[生化微生物免疫研究所] 博碩士論文

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