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Please use this identifier to cite or link to this item: http://ir.hwai.edu.tw:8080/ir/handle/310996100Q/1634

Title: Chalcone 抑制人類膀胱癌細胞侵襲及移動之機制探討
Study of the inhibitory effect and mechanism of chalcone on human bladder cancer cells invasion and migration
Authors: 李建輝
Lee, Chien-Hui
Keywords: 轉移
bladder cancer
Date: 2013
Issue Date: 2013-11-01 10:36:32 (UTC+8)
Abstract: Chalcone 是由明日葉所萃取出來的類黃酮抗氧化物,具有抗菌、抗發炎的功效,近來有研究指出 chalcone 已被應用於抗癌的研究。本篇研究主要探討 chalcone 是否可以有效地抑制人類膀胱癌細胞的轉移及侵襲能力,進一步探討相關的分子作用機制。在體外實驗中,為了要觀察 chalcone對於癌細胞轉移能力的影響。我們選取了一株俱有高度轉移能力的人類膀胱癌 T24 細胞,分別處理不同濃度的 chalcone 來探討此藥物對於癌細胞移動性及侵入能的影響。首先利用 wound healing assay 及 Boyden chamber assay ,我們發現chalcone 可以抑制 T24 膀胱癌細胞的移動性及侵入性,在 gelatin zymography、casein-plasminogen zymography 和 polymerase chain reaction 中也發現 chalcone 可以抑制 T24 細胞中MMP-2、MMP-9 及 u-PA 的活性及
messenger RNA 的表現。為了進一步探求 chalcone 抑制 T24 細胞侵入的機轉,利用西方墨點法,我們發現訊息傳遞途徑中的FAK、ERK1/2、p38、JNK1/2 和 Akt 的磷酸化表現皆會受到 chalcone 所抑制。然而這些蛋白的活化是否調控著 T24 細胞的侵襲能力,透過專一性抑制劑:U0126、SB203580、SP600125 及 LY294002 幫助我們釐清了 ERK1/2、p38、JNK1/2 及 PI3K 路
徑可以調控 T24 細胞 MMP-2、MMP-9 及u-PA 的表現。另外在實驗中也證實 small GTPase family,如:Ras、Rac-1、Cdc42、RhoA、RhoB 的蛋白表現量也會受到 chalcone 所抑制。此外,核蛋白中 NF-κB、c-Fos、c-Jun 的表現皆會受到 chalcone 所抑制。綜合上述所有的實驗結果,chalcone 可能是透過FAK/MAPK 和 FAK/PI3K/Akt signal pathway 來影響下游的轉錄因子
NF-κB 的活性,進而影響分泌 MMP-2 、 MMP-9 及 u-PA,最後抑制 T24 細胞的侵襲及移動。
Chalcone is a flavonoid antioxidant extracted from Angelica keiskei koidzumi. It has various effect such as antibacterial and anti-inflammatory activities. In recent studies, chalcone has shown its anti-cancer property. The purpose of this study is to investigate the inhibitory effect and mechanism of
chalcone on human bladder cancer cells metastasis in vitro. We chosed a highly metastastic human bladder T24 cancer cell line which was treated with various concentrations of chalcone to investigate the potential of inhibiting cancer cell migration and invasion. First, we found that chalcone inhibited T24 cells migration and invasion via wound healing assay and Boyden chamber assay. MMP-2, MMP-9, u-PA activity and messenger RNA level were also inhibited by chalcone via gelatin zymography, casein-plasminogen zymography and polymerase chain reaction. In the signal transduction pathway, we found that the phosphorylation of the FAK, ERK1/2, p38, JNK1/2 and Akt were inhibited by chalcone via Western blotting. To verify the activation of above proteins whether regulated T24 metastatic ability, we used specific inhibitors:U0126, SB203580, SP600125 and LY294002 to clarified that the signal transduction of FAK, ERK1/2, p38, JNK1/2 and PI3K/Akt regulated MMP-2 , MMP-9 and u-PA expression. On the other hand, chalcone inhibited the protein level of Ras, Rac-1, Cdc42, RhoA and RhoB with concurrent reduction in the expression level of NF-κB, c-Fos and c-Jun. In the present study, we demonstrated that chalcone inhibited T24 cells might be through the FAK/MAPK and FAK/PI3K/Akt signal pathways and exerted inhibitory effect on the expression of NF-κB transcription factor, MMP-2, MMP-9 and u-PA, afterward inhibited migration and invasion in T24 human bladder cancer cell. This study suggests a possible role of chalcone in bladder cancer therapy.
Appears in Collections:[生物科技系暨生物醫學研究所] 博碩士論文

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