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    請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/59477


    題名: 探討新型蛋白去乙醯酶抑制劑OHC-2對人類非小細胞肺癌細胞增生及單核球之作用
    Investigation of Mechanism of a New HDAC Inhibitor OHC-2 on Human Non Small Cell Lung Cancer Cell Proliferation and Monocytic Activation
    作者: 劉莉雅
    Liu, Li-Ya
    貢獻者: 謝政穎
    關鍵詞: 肺癌;組織蛋白去乙醯酶;抑制劑;抗增生
    A549;HDACi;p21
    日期: 2015-06-23
    上傳時間: 2020-08-28 15:48:39 (UTC+8)
    摘要: 肺癌在全球癌症死亡率中位居首位且其發生率有逐年增加的趨勢，又以非小細胞肺癌占大多數。在腫瘤微環境中，癌細胞會藉由表現基質金屬蛋白酶及釋放細胞激素以促進浸潤及癌症的惡化。在本研究中選用人類肺腺癌細胞株A549及人類單核球細胞株THP-1探討histone deacetylase inhibitor (HDACi)-衍生物OHC-2對細胞增生之影響。結果顯示OHC-2會增加acetyl alpha-tubulin、acetyl SMC3及acetyl histone H3 protein的表現。此外，OHC-2可抑制A549細胞停滯在G2/M期且可負調控細胞週期蛋白Cyclin A2, Cdk2及正調控Cyclin B1之表現亦可增加p21及減少PARP蛋白的表現。再者本實驗也發現Akt相關路徑可讓survivin的表現減少。OHC-2對A549細胞有抗增生及DNA damage的現象。OHC-2亦會減少pATM及pATR蛋白表現及抑制HSP90活性。另一方面，OHC-2可抑制LPS誘導THP-1之MMP-9活性。另外，OHC-2對THP-1在LPS的刺激下可使IL-6分泌減少及IL-1beta分泌增加，然而單純給予OHC-2不會影響THP-1對IL-1beta的分泌。綜合上述結果顯示，OHC-2可抑制癌細胞增生及浸潤，此發現有助於未來癌症治療藥物的開發。
    Lung cancer ranks first in cancer mortality in the worldwide, and its incidence rate has increased year by year. In the tumor microenvironment, cancer cells promote tissue infiltration and disease progression through expressing matrix metalloproteinase and viarious cytokines. In this study, human lung adenocarcinoma epithelial cell line A549 and human monocyte cell line THP-1 are selected as the models to investigate the effects of HDACi-derived products: OHC-2 on cell proliferation. These result show OHC-2 upregulated acetyl alphatubulin, acetyl SMC3 and acetyl histone H3 protein expression. In addition, OHC-2 inhibited A549 cells growth and induced G2/M arrest, and downregulated expression of Cyclin A2, Cdk2, upregulated expression of Cyclin B1 and increased p21, reduced PARP protein expression. Also, OHC-2 decreased survivin through Akt-depedent pathway. OHC-2 causes anti-proliferation and DNA damage in A549 cells. Finally, OHC-2 inhibits pATM, pATR protein expression and HSP90 activation. On the other hand, OHC-2 suppresses MMP-9 activity after LPS-stimulated THP-1 cells. In particular, the data shows that OHC-2 suppresses IL-6 and enhances IL-1beta secretion by LPS-stimulated THP-1 cells.However OHC-2 doesn’t affect the secretion of IL-1beta in THP-1 cells. These result suggest that OHC-2 inhibits proliferation and infiltration in cancer cells. It may be utilize as the therapeutic agent for lung cancer.
    描述: 碩士
    指導教授:謝政穎
    委員:顧記華
    委員:陳炳常
    委員:潘秀玲
    資料類型: thesis
    顯示於類別:[醫學科學研究所] 博碩士論文

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