紅麴山藥酒精萃取物緩解放射線治療衍生之副作用

The moderation of radiotherapy side effects by ethanol extract of red mold dioscorea

黃之丞(Chih-Chen Huang)

指導教授 ： 潘子明

國立臺灣大學/生命科學院/微生物與生化學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.02542

摘要

放射線治療為有效控制腫瘤的癌症治療方式。放射線雖然能抑制癌細胞增生和毒殺癌細胞，但也會因發炎與纖維化反應而對正常組織造成傷害。因此，如何減少放射線治療衍生的副作用為一重要課題。紅麴 (Monascus) 為中國傳統發酵真菌，運用在食品上已有數千年的歷史，其二次代謝產物經現代科學研究證實具有降低膽固醇、抗發炎、抗腫瘤與抑制腫瘤轉移等功效，適合輔助放射線治療減輕副作用。本研究分為體內動物實驗和體外細胞實驗兩部分，探討紅麴山藥酒萃物 (ethanol extract of red mold dioscorea, RMDE) 是否具有緩解放射線治療衍生的副作用之功效。實驗結果顯示，RMDE 的餵食，能增加放射線治療後小鼠的體重和攝食量，並且抑制腫瘤的復發。此外，RMDE 能緩解放射線所引起脾臟腫大之情形，血清促發炎激素 (tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β; interleukin-6, IL-6)、促纖維化激素 (transforming growth factor-β1, TGF-β1) 和血管內皮生長因子 (vascular endothelial growth factor, VEGF) 也因 RMDE 的餵食，具有顯著性降低的現象。由組織病理切片結果得知，RMDE 對於小鼠肺、肝和腎臟並無任何的影響。在細胞實驗方面，RMDE 中的 ankaflavin 和 citrinin 對於小鼠皮膚初代細胞和 B16-F0 並不具明顯抑制效果，而 monascin 對於小鼠皮膚初代細胞不具明顯抑制，但可以有效抑制癌細胞 (B16-F0) 的生長。在放射線誘導細胞損傷模式中，紅麴山藥酒萃物和其功效成分 ankaflavin 能抑制放射線所誘發 TNF-α、IL-1β、IL-6 和 TGF-β1 mRNA 大量表現之情形，monascin 對 IL-1β、IL-6 和 TGF-β1 mRNA 表現具抑制作用，但對於 TNF-α 則不具影響。綜合以上，紅麴山藥酒萃物能緩解放射線治療衍生的副作用，適合輔助臨床癌症治療。

關鍵字

放射線治療 ； 紅麴 ； 副作用 ； 發炎 ； 纖維化

並列摘要

Radiotherapy is frequently used as part of cancer treatment to achieve tumor control. Apart from inducing anti-proliferative and cell-killing effects in tumor tissue, radiotherapy also provokes normal tissue damage such as inflammation and fibrosis. Therefore, how to alleviating the side effects of radiotherapy is a crucial problem. The Monascus species is a Chinese traditional fermentation fungus used on food for over thousands of years in China. The secondary metabolites of Monascus in the contemporary research were confirmed the suppression cholesterol production, anti-inflammation, anti-tumor and suppression tumor metastasis. Accordingly, Monascus metabolites can apply to radiotherapy to alleviate the side effects. In this study, we investigated whether ethanol extract of red mold dioscorea (RMDE) attenuates radiation-induced normal tissue damage in vivo and in vitro. Results showed that oral administration of RMDE can increase animal body weight and food intake but suppress tumor regression. Besides, radiation-induced splenomegaly was significantly alleviated by RMDE. The pro-inflammatory (i.e. tumor necrosis factor-α, TNF-α; interleukin-1β, IL-1β; interleukin-6, IL-6), pro-fibrotic (i.e. transforming growth factor-β1, TGF-β1) and angiogenesis (i.e. vascular endothelial growth factor, VEGF) maker in serum of RMDE treatment group was significantly lower than control group. Furthermore, the results of histopathological slices of lung, liver and kidney in each group did not show any significant difference from histopathological finding. In vitro assays, the cytotoxic assay showed that RMDE have more cytotoxic to B16-F0 cells than skin primary cells. Ankaflavin, monascin and citrinin are non-effect in skin primary cells. Monascin can inhibit B16-F0 proliferation. According to the radiation-induced cell damage model, RMDE and ankaflavin treatment can inhibit TNF-α, IL-1β, IL-6 and TGF-β1 mRNA expression and monascin can inhibit IL-1β, IL-6 and TGF-β1 mRNA expression but not TNF-α. These features of RMDE have made it an attractive candidate to moderate the side effects in clinical radiotherapy.

並列關鍵字

radiotherapy ； Monascus ； side effects ； inflammation ； fibrosis

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