靈芝防治癌症之初期臨床前療效評估

Pre-clinical effects of Ganoderma lucidum on cancer treatment

陳曉君(Hsiao-Chun Chen)

指導教授 ： 鄧文炳

臺北醫學大學/口腔醫學院/生物醫學材料研究所/碩士(2008年)

摘要

癌症是世界各國醫學界的重大議題，目前並沒有能根除癌細胞的有效治療方式，而將中草藥應用於癌症治療為目前新興的研究方向之一。靈芝的學名為Ganoderma lucidum，是一種木本擔子菌類，已被研究證實有立即的細胞毒性且可有效抑制多種癌症細胞的生長。本論文主要是人類子宮頸癌細胞HeLa及非小細胞肺癌H441GL為癌細胞之模式，研究酒萃靈芝抑制惡性腫瘤的效果及機制探討，同時利用本實驗室偵測癌症逆轉現象之篩選平台技術，進一步研究酒萃靈芝是否兼具有抑制惡性腫瘤以及癌症逆轉之特性，並且利用非侵入式活體分子基因造影系統同步即時觀察惡性腫瘤細胞在生物活體內之變化。第一部份實驗以酒萃靈芝處理人類子宮頸癌細胞HeLa，結果顯示酒萃靈芝會抑制子宮頸癌細胞HeLa之鹼性磷酸酶(Alkline phosphates)表現，具有癌症逆轉之特性，且細胞生長受到抑制，細胞週期於sub-G1 phase之百分比明顯增加，細胞致癌蛋白E7及凋亡前趨蛋白procaspase 3表現量下降，細胞遷徙能力受到抑制。在動物體內腫瘤生成實驗方面，長期餵食酒萃靈芝1000 mg/kg/mice/day可以有效抑制腫瘤細胞於實驗動物體內的生成。第二部份實驗結果顯示，酒萃靈芝能抑制人類肺癌細胞H441GL之生長，隨著藥物濃度增加而cyclin E蛋白表現量上升，使細胞週期停滯在G0/G1 phase，另外細胞遷徙能力亦會下降。在動物實驗方面，長期給予酒萃靈芝1000 mg/kg/mice/day具有抑制H441GL腫瘤生成之能力。本研究顯示酒萃靈芝能夠降低子宮頸癌細胞HeLa及非小細胞肺癌細胞H441GL之生長能力，並使細胞週期停滯，且能有效抑制腫瘤於活體動物體內之生成，另外，非侵入式分子影像活體造影技術可以準確且快速的分析活體內酒萃靈芝對於腫瘤之功效。

關鍵字

靈芝 ； 子宮頸癌 ； 非小細胞肺癌 ； 細胞週期 ； 癌症逆轉 ； 非侵入式分子影像活體造影系統

並列摘要

Cancer is the leading cause of deaths worldwide. Lately, Chinese herbal medicine has been used increasingly in allopathic medicine. Ganoderma lucidum, also known as “LingZhi”, is a woody Basidiomyceyes mushroom which belongs to the Ganodermaceae family. Previous studies demonstrated that Ganoderma lucidum ethanol extracts exerted immunomodulating, antioxidative, anticancer activity and cytotoxicity to cancer cells. The objective of this research was to identify the bioactive compounds in ethanol extracts of Ganoderma lucidum which contain anti-tumor activities. In our study, we demonstrated that Ganoderma lucidum ethanol extracts inhibited proliferation of human cervical cancer, HeLa cells, in a dose-dependent fashion. Ganoderma lucidum ethanol extracts treatment led to an increase number of HeLa cells in sub-G1 phase as well as the induction of apoptosis. Ganoderma lucidum ethanol extract also increased reversion frequency by decreasing the expression of oncoprotein E7 and alkaline phosphatase activity in HeLa cell. Human non-small cell lung cancer cell line, H441GL cells, which contains a firefly luciferase gene was used for non-invasive in vivo tumor volume monitoring and assessement of novel therapeutics. In this part, we demonstrated that Ganoderma lucidum ethanol extract induced the expression of cyclin E protein and caused H441GL cells to arrest in G0/G1 phase thereby inhibiting their proliferation. In vivo animal experiments, we demonstrated that feeding Ganoderma lucidum treatment yielded a much less aggressive tumor growth than the control group. Although further studies are requied, the present work suggests that Ganoderma lucidum may have beneficial effects in treating both cervical cancer cells, HeLa, and NSCLC such as H441GL carcinoma. Non-invasion bioluminescent imaging system provides a functional way of monitoring tumor volume in animal model. Ganoderma lucidum may raise the possibility of continuing management of some cancers as a chronic condition in which the malignancy is constrained.

並列關鍵字

Ganoderma lucidum ； Cervical cancer ； Non-small cell lung cancer ； Cell cycle ； Cancer reversion ； Non-invasive molecular imaging system

參考文獻

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