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  • 學位論文

氰肽氟苯胺對非小細胞肺癌細胞之影響與相關機制探討

The study of escitalopram oxalate and its related mechanisms on non-small cell lung cancer cells

指導教授 : 曾博修

摘要


氰肽氟苯胺是一種用於治療重度憂鬱 (MDD)、廣泛性焦慮症 (GAD) 的選擇性血清素再攝取抑制劑 (SSRI),透過抑制血清素進入神經末梢突觸前的再回收,這種藥物會增強血清素在中樞神經系統中的活性。有研究顯示,SSRIs在不同癌細胞對於細胞增殖 (Cell proliferation)、細胞週期 (Cell cycle)、細胞凋亡 (Cell apoptosis) 具有影響。因此我們想了解氰肽氟苯胺對於人類非小細胞肺癌 (NSCLC) 是否有抑制效果。實驗結果發現當非小細胞肺癌細胞處理氰肽氟苯胺後,其細胞增殖、存活率、移動能力 (migration) 及侵襲能力 (invasion) 會顯著性的降低,並且透過流式細胞儀分析發現氰肽氟苯胺會增加細胞週期中Sub G1的比率。此外,西方墨點法分析結果發現Bax、Apaf-1、caspase-3、NF-kB及p21的表現量增加,而cyclin D1的表現量降低,證實氰肽氟苯胺是透過誘導細胞凋亡和抑制細胞週期。因此,在未來氰肽氟苯胺也許可以成為治療肺癌另一個新的選擇。

並列摘要


Escitalopram oxalate is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). By inhibiting the reuptake of serotonin into presynaptic nerve endings, this drug enhances the activity of serotonin in the central nervous system. According to previous studies that SSRIs affects on the cell proliferation, cell cycle and cell apoptosis in various types of cancer. Hence, we want to investigate whether escitalopram oxalate has inhibition effects on human non-small cell lung cancer (NSCLC). We found that of NSCLC cells treated with escitalopram oxalate exhibited significantly reduced cell proliferation, cell viability, migration and invasion. Meanwhile, flow cytometry analysis revealed that exposure of NSCLC cells to escitalopram oxalate resulted in increased Sub G1 peak. Furthermore, Western blotting showed that the expression of Bax, Apaf-1, caspase-3, NF-kB and p21 were increased in NSCLCS cells treated with escitalopram oxalate, cyclin D1 was reduced. This study showed that escitalopram oxalate induce NSCLC apoptosis and Cell cycle arrest and suggest that escitalopram oxalate in the future may be useful to provide an alternative choice in treatment of NSCLC.

參考文獻


50. 台北市立聯合醫院癌症防治研究發展中心網站
6. American Psychiatric Association 2000a, p. 355
7. American Psychiatric Association 2000a, pp. 419–20

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