異烏藥內酯對人類肺癌非小細胞肺癌A549細胞之作用機制探討

The molecular mechanism of isolinderalactone in human non small cell lung cancer A549 cells

張維安(Wei-An Chang)

指導教授 ： 郭柏麟

高雄醫學大學/醫學院/臨床醫學研究所/碩士(2014年)

摘要

肺癌是全世界盛行率及死亡率最高的一種癌症，每年新增病例超過一百三十萬人，且每年病例數有逐漸攀升的趨向，而肺癌死亡率的增加也居所有癌症的首位。在台灣，肺癌目前仍名列癌症死亡率的第一位，並且有逐年增加的趨勢。所以，開發一可防止肺癌發生、或可有效降低抗藥性、或增加肺癌細胞對化學藥物敏感性的藥物乃當務之急。本研究分析異烏藥內酯(isolinderalactone)在肺癌細胞之細胞凋亡和細胞週期作用，更深入探究p21/WAF1、Fas/APO-1 receptor、Fas ligand以及caspase-8等分子的表現情形。我們發現異烏藥內酯(isolinderalactone)對於人類非小細胞肺癌A549細胞有增生抑制效果，証實了isolinderalactone可以誘發p21的表現增加，進而導致A549的細胞週期停滯，同時實驗結果也支持Fas/sFasL細胞凋亡系統在isolinderalactone引發的A549細胞凋亡扮演重要的角色。

關鍵字

異烏藥內酯 ； 人類肺癌非小細胞肺癌 ； 細胞凋亡 ； p21 ； Fas ； soluble Fas liganc

並列摘要

Lung cancer is the leading cause of death related to cancer in the world today. In Taiwan, lung cancer is also the malignancy that is a major cause of death. Investigating the mechanism of apoptosis of lung cancer is very important to the treatment of lung cancer. In this study, we first demonstrated that isolinderalactone has anticancer effects in human non-small cell lung cancer A549 cells. We assayed the effect of isolinderalactone on apoptosis, cell cycle distribution p21 levels, Fas receptor and soluble Fas ligand (sFasL) to survey the mechanism of isolinderalactone’s anticancer effect. Finally, we proved that isolinderalactone can induce p21, and then cause the cell cycle arrest of A549 cells. Our data also showed that the Fas/sFasL apoptotic system plays an important role in the mechanism of isolinderalactone-induced apoptosis of A549 cells. These novel findings demonstrate that isolinderalactone can cause the cell cycle arrest of A549 cells by induction of p21 and induce apoptosis of human NSCLC A549 cells through the Fas/sFasL- mediated apoptotic pathway activation.

並列關鍵字

isolinderalactone ； non-small cell lung cancer ； p21 ； Fas ； soluble Fas ligand ； apoptosis

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