Akt-targeting compounds inhibit cellular proliferation and induce apoptosis in zebrafish hosting lung cancer xenografts / 以斑馬魚異體移植模式探討Akt-標靶化合物對抑制肺癌細胞增生及促進細胞凋亡

碩士 / 高雄醫學大學 / 生物科技學系碩士班 / 102 / Lung cancer is the leading cause of cancer death in males and females worldwide. The non-small cell lung cancer (NSCLC) accounts for at least 85% lung cancer and easily metastasizes to other organs such as brain, liver and bone. Akt, a serine/threonine-specific protein kinase, which is known to regulate various cellular physiologies, including cellular survival, proliferation, migration and angiogenesis. Constitutive phosphorylation or over-expression of Akt was frequently observed in NSCLC cells. Recently studies showed that Akt targeting may be a promising approach for lung cancer treatment. Besides, quinone compounds are formally derived from aromatic compounds such as benzene or naphthalene. Quinone derivative was reported to exert the antitumor activity. Accordingly, we used bioinformatics approaches to screen twelve quinone-based compounds which exhibit Akt-targeting potential. In the preliminary results, we found that one of the Akt-targeting compounds quinone X1, exerts a moderate cytotoxicity towards NSCLC tumor H1299 cells. Concomitantly, the Akt-targeting compound quinone X1 causes the polyploidy and DNA double strand breaks associates ROS in H1299 cells. A significant apoptotic population was observed in quinone X1-treated H1299 cells. Additionally, quinone X1 inhibits both the invasion and colony formation of H1299 cells. Consistently, the zebrafish xenograft assay also validates the anti-lung tumor effects of quinone X1. Accordingly to these above observations, our present work suggests that the application of Akt-targeting compound may be a promising approach for lung cancer treatment.

Identiferoai:union.ndltd.org:TW/102KMC05111004
Date January 2014
CreatorsMei-Chien Lu, 盧美潔
ContributorsChien-chih Chiu, 邱建智
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format102

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