α-Chaconine抑制肺腺癌細胞侵襲及轉移之研究

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Title:	α-Chaconine抑制肺腺癌細胞侵襲及轉移之研究 The inhibitory effect of α-chaconine on the invasion and migration of lung adenocarcinoma cells
Authors:	施元薇 Yuan-Wei Shih
Contributors:	王朝鐘陳品晟嘉南藥理科技大學：生物科技研究所
Keywords:	細胞外基質轉移人類肺腺癌細胞 α-Chaconine Metastasis Human lung adenocarcinoma cells
Date:	2007
Issue Date:	2008-12-03 11:15:21 (UTC+8)
Abstract:	α-Chaconine是由茄科馬鈴薯芽眼中所萃取出來的天然固醇類生物鹼，近年來有研究指出α-chaconine具有抗癌的特性，其中包括了細胞凋亡的研究。可是，α-chaconine對癌細胞的轉移方面的影響目前尚不清楚。本研究主要探討α-chaconine是否可以有效地抑制人類肺腺癌細胞的侵入能力及移動性，並進一步探討相關的分子作用機轉。在體外實驗中，為了要觀察α-chaconine對癌細胞轉移能力的影響，我們選取了一株具有高度轉移能力的人類肺腺癌細胞：A549細胞，分別處理不同濃度的α-chaconine來探討此藥物對A549細胞侵入及移動能力的影響。首先，藉由wound healing assay及Boyden chamber assay，我們發現α-chaconine可以抑制A549細胞侵入及移動能力，在gelatin zymography中也發現α-chaconine可以抑制A549細胞中MMP-2及MMP-9的活性。為了更進一步探求α-chaconine抑制A549細胞侵入的機轉，利用西方墨點法，發現在訊息傳導路徑中的 p-JNK、PI3K/p-Akt明顯地受到α-chaconine的抑制，在實驗中也證實small GTPases，例如: Ras、Rac-1、Cdc42、RhoA) 的蛋白表現會受到抑制；相反地，RhoB蛋白表現量會隨?chaconine處理而增加。另外核蛋白中，例如：NF-κB、c-Fos、c-Jun的蛋白表現會因α-chaconine的處理而受到抑制。此外，利用EMSA分析，發現A549細胞在處理α-chaconine之後，NF-κB與DNA上NF-κB response element 的結合能力明顯的下降，然而AP-1之轉錄活性並沒有明顯的變化。因此證實α-chaconine可能是透過PI3K/Akt這條路徑進而降低轉錄因子NF-κB 的結合能力以及減少MMP-2/MMP-9的表現進而去抑制A549細胞侵襲及移動能力。所以由目前已完成的上述各種實驗結果證實了α-chaconine可能有效地抑制A549 細胞的侵入及移動能力，並期望它在癌症治療上能成為有效的化學治療藥物。 α-chaconine isolated from Solanum tuberosum Linn., is a naturally occurring steroidal glycoalkaloid in potato sprouts. In recent studies, α-chaconine has shown to have various anti-carcinogenic properties, including inducing cell apoptosis. However, the in vitro effect of α-chaconine on metastasis of cancer cells was still unclear. The aim of this study is to investigate the inhibitory effect and mechanism of α-chaconine on lung adenocarcinoma cells metastasis in vitro. We chosed a highly metastatic human lung adenocarcinoma cell line：A549 cell, which was treated with various concentrations of α-chaconine to elucidate the potential of inhibiting A549 cells invasion and migration. First, we found that α-chaconine inhibited A549 cells invasion/migration via wound healing assay and Boyden chamber assay; MMP-2 and MMP-9 activity were also inhibited by α-chaconine via gelatin zymography assay. In the signal transduction pathway, our data revealed that α-chaconine inhibited p-JNK and PI3K/p-Akt with concurrent reduction in the protein level of Ras, Rac-1, Cdc42 and RhoA by Western blotting, whereas the protein level of RhoB presented a progressive increase. Otherwise, α-chaconine-treated A549 cells showed tremendously decreased in the expression level of NF-κB, c-Fos and c-Jun. In addition, α-chaconine significantly inhibited the binding abilities of transcription factors NF-κB to NF-κB response element by the electrophoretic mobility shift assay (EMSA). AP-1 transcripition activity did not show a noticeable change. In the present study, we demonstrated that α-chaconine inhibited A549 cells might be through PI3K/Akt signaling pathway and exerted inhibitory effect on NF-κB transcription factor and decreased DNA binding activity of NF-kB, afterward decreased MMP-2 and MMP-9 expressions. The results demonstrate that α-chaconine was able to inhibit invasion/migration in A549 human lung cancer cell line and might, therefore, be effective on chemotherapeutic treatment.
Relation:	校內校外均不公開
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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