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    題名: 探討真菌固醇結合兩性黴素 B 對人類肝癌細胞之抑制作用
    Inhibition of human hepatocellular carcinoma cells by fungal sterols combined with amphotericin B
    作者: 林郁淳
    Lin, Yu-Chun
    貢獻者: 醫學科學研究所
    關鍵詞: 靈芝;麥角固醇;真菌固醇;兩性黴素 B;肝癌
    Ganoderma lingzhi;ergosterol;fungal sterols;amphotericin B;hepatocellular carcinoma
    日期: 2016-01-04
    上傳時間: 2021-01-07 10:08:18 (UTC+8)
    摘要: 靈芝是一種在世界上被廣泛地栽培和使用的藥用菇類,具有許多藥理特性,包含抗發炎、保肝、降血糖、降血脂、調節免疫以及抗氧化活性。靈芝酒萃物所含的主要活性物質,如三萜類與固醇,對於多種人類癌細胞株皆具有抗癌功效。過去的文獻指出,麥角固醇提高老鼠血癌細胞對於兩性黴素 B 的敏感度,本篇研究欲闡明靈芝酒萃物 (Ganoderma lingzhi ethanolic extract) 中所含的主要活性物質併用兩性黴素 B 對人類肝癌細胞抑制作用之可能機制。首先,利用酸鹼水溶液萃取的方式將靈芝酒萃物分為酸性層 (Ganoderma lingzhi ethanolic extract acid fraction) 及非酸性層 (Ganoderma lingzhi ethanolic extract non-acid fraction),接著使用薄層層析法分離靈芝酒萃物與各分層進而比對出麥角固醇 (ergosterol) 和麥角醯胺 (ergone),研究結果顯示,預處理麥角固醇或麥角醯胺提升兩性黴素 B 的抑癌功效,此外,預處理麥角固醇結合兩性黴素 B 誘發細胞週期停滯、細胞週期抑制蛋白 P21 與 P27 表現以及自噬作用指標蛋白 P62 與 LC-3 A/B II 活化。綜合以上所述,麥角固醇或麥角醯胺併用兩性黴素 B 具有潛力,值得進一步開發並做為肝癌病患有效且安全的療法。
    Ganoderma lingzhi is a widely cultivated and used medicinal mushroom with several pharmacological functions such as anti-inflammation, liver protection, antidiabetics, antihyperlipidemia, immunomodulation, and antioxidative activities. The bioactive compounds of Ganoderma lingzhi ethanolic extract include mainly triterpenes and sterols that possess antitumor effects in various human cancer cell lines. In a previous study, ergosterol conferred sensitivity to amphotericin B in mouse leukemia cells. The aim of this study is to elucidate the mechanism of inhibition of human hepatocellular carcinoma cells by bioactive compounds from Ganoderma lingzhi ethanolic extract combined with amphotericin B. Firstly, Ganoderma lingzhi ethanolic extract was fractionated into acid fraction and non-acid fraction by acid-base extraction, and then thin layer chromatography was used for the separation and identification of compounds such as ergosterol and ergone. In the present study, pretreatment with ergosterol or ergone enhanced the tumor suppression efficiency of amphotericin B. Besides, pretreatment of ergosterol in combination with amphotericin B induced cell cycle arrest, upregulation of cell cycle inhibitors, P21 and P27, and activation of autophagy indicator, P62 and LC-3 A/B II. These results together suggested that ergosterol integrated with amphotericin B has potential to be further developed as an effective and safe treatment for liver cancer patients.
    描述: 碩士
    指導教授:李玲玟
    委員:許明照
    委員:王靜瓊
    委員:戴承正
    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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