請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/20171
標題: Tamoxifen調控的細胞移動及EMT與tNOX蛋白質表現間的關係
Tamoxifen induces cell migration and EMT in association with tNOX (tumor-associated NADH oxidase) upregulation
作者: 林禹涵
Lin, Yu-Han
關鍵字: tNOX
NADH 氧化酶他莫昔芬
tamoxifen
migration
移行
出版社: 生物醫學研究所
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摘要: Tumor-associated NADH oxidase (tNOX) 為癌細胞膜上的一種蛋白質,且由過去的研究得知tNOX的表現及酵素活化,與癌細胞的生長、移行能力有關。於非轉型的細胞過度表現tNOX,發現會誘發細胞轉型,且使細胞的侵襲能力增加。然而,使用不同種的藥物處理,例如: EGCg,capsaicin等,發現明顯抑制了tNOX的表現及活性,且引發細胞凋亡,進一步降低癌細胞在生長能力。Tamoxifen 為一種抗雌激素的乳癌抗癌藥物,被研究於乳癌已幾十年,由累積下來眾多的文獻得知,藉由影響細胞內多種蛋白質的表現與活性來影響細胞在生長及移行、轉移能力,tamoxifen可以進一步抑制乳癌。但是,我們對於tamoxifen 處理在其他癌症及對tNOX造成的影響並不了解,所以於本篇研究中,我們使用肺癌細胞株及大腸癌細胞株做為實驗模式,進一步去探討以tamoxifen的處理,對 tNOX的影響及肺癌與大腸癌細胞的變化。 由實驗結果得知,tamoxifen處理明顯會抑制肺癌細胞A549的生長,藉由引發細胞週期遏止在G1 phase及細胞凋亡。此外我們也發現以1,5 μM的tamoxifen處理時,細胞移行的能力會增加,且細胞的epithelial markers 減少,mesenchymal markers 增加,此現象在5 μM tamoxifen則最為明顯。此外,tamoxifen處理對於tNOX的表現在1,5 μM為正向調控,且在5 μM tamoxifen則增加最多,至10 μM則與5 μM相比較,未隨dose dependent增加,為減少趨勢,至20 μM tamoxifen處理而明顯被抑制。進一步在大腸癌細胞HCT116以1,5 μM tamoxifen處理時,細胞明顯有進行EMT的現象,epithelial markers減少及mesenchymal markers 增加,且tNOX的表現為正向調控,在5 μM tamoxifen處理則增加最多,至10 μM tamoxifen處理而有減少的趨勢,至20 μM tamoxifen處理而明顯被抑制。 由於在過去的研究指出,tNOX會增加細胞的移行能力,在這個研究也發現,1,5 μM tamoxifen的處理肺癌細胞株A549及大腸癌細胞株HCT116,造成tNOX的表現增加且引發EMT及細胞移行能力增強,因此我們推測tamoxifen處理在肺癌細胞株A549及大腸癌細胞株HCT116引發細胞移行能力增強,可能與 tNOX 的表現量有關。
Tumor-associated NADH oxidase (tNOX) is a membrane protein expressed in transformed cells. Based on previous studies, tNOX protein level and activity are associated with the growth and capability of migration in cancer cells. In particular, overexpression of tNOX in non-transformed cells, induces cells transformation and invasion. However, different anti-cancer drugs, for example, EGCg and capsaicin, are shown to inhibit tNOX expression and activity, leading to decreased cell growth. Tamoxifen is an anti-breast cancer drug that has been investigated for many years. Accumulating data have suggested that tamoxifen influences cells growth and migration through many targets in cells, resulting in inhibition in breast cancer. However, little is known for the effects of tamoxifen on tNOX protein in A549 and HCT116 cells. In this study, our results that tamoxifen induces an inhibition in growth of A549 cells resulting from cell cycle arrest and apoptosis. Surprisingly, we observed an up-regulation of tNOX associating enhanced cell migration and EMT when cells were treated with 1,5 μM tamoxifen in A549 and HCT116 cells. Taken together, we propose that tNOX protein is important for cancer cell survival as well as cellular responses toward anticancer drugs.
URI: http://hdl.handle.net/11455/20171
其他識別: U0005-1608201114235200
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