探討靈芝多醣改善順鉑合併使用歐洲紫杉醇於肺癌及其不良副作用

Study of Ganoderma polysaccharide on Cisplatin and Docetaxel-induced Side Effects for Lung Cancer therapy

李孟霖(Meng-Lin Lee)

指導教授 ： 柯俊良 ； 詹明修

中山醫學大學/醫學院/生化微生物免疫研究所/碩士(2019年)

https://doi.org/10.6834/CSMU201900154

摘要

順鉑 (Cisplatin) 與歐洲紫杉醇 (Docetaxel) 常用於治療肺癌患者，但所產生的不良副作用像厭食/惡病質、嗜中性白血球下降及貧血會最終導致提早終止化學療程。先前研究指出靈芝多醣 (Ganoderma polysaccharide) 中(1,3)(1,6)-β-D-葡聚醣能活化抗腫瘤免疫系統。本研究使用小鼠模式及體外實驗中透過MTT測定，發現雙鶴靈芝-輔健靈芝 (Liz-H) 可以增加順鉑和歐洲紫杉醇對Lewis肺癌細胞 （LLC） 的毒殺作用，西方墨點法發現Liz-H增加順鉑和歐洲紫杉醇中所誘導的細胞凋亡cleaved caspase-3蛋白表現。在小鼠實驗中，餵食Liz-H降低了小鼠的腫瘤大小並減少了脾臟中由腫瘤誘發的骨髓抑制細胞 (Myeloid-derived suppressor cells) ，餵食Liz-H恢復了順鉑和歐洲紫杉醇誘導的體重減輕。Liz-H改善了順鉑和歐洲紫杉醇治療後所誘導的肌肉蛋白降解基因 （MURF-1，Atrogin-1） 上升和肌肉合成基因 （MyoD，Myogenin） 下降。我們還觀察到餵食Liz-H在順鉑和歐洲紫杉醇治療的小鼠中恢復了嗜中性白血球低下症和血清生化胺基轉氨酶。本研究數據顯示，靈芝多醣 （Liz-H） 可以改善順鉑和歐洲紫杉醇誘導的肺癌治療及其不良副作用。

關鍵字

靈芝多醣 ； 肺癌 ； 順鉑 ； 歐洲紫杉醇 ； 副作用

並列摘要

Cisplatin and Docetaxel are used in the treatment of lung cancer, but the adverse effects, such as anorexia/cachexia, neutropenia and anemia, of these drugs may lead to premature termination of chemotherapy. Previous studies demonstrated (1,3)(1,6)-β-D-glucan of Ganoderma polysaccharide induced anti-tumor immunity. This study investigated the efficacy of Liz-H, a Ganoderma polysaccharides, on side effects induced by Cisplatin and Docetaxel in a mouse model. In vitro, Liz-H increased cytotoxicity which induced by Cisplatin and Docetaxel in Lewis Lung Carcinoma cells (LLC) by MTT assay. Liz-H increased that of Cisplatin and Docetaxel ecilited protein expression of cleaved caspase-3 by Western blot. In vivo, oral administration of Liz-H reduced the tumor size of mice and decreased Myeloid-derived suppressor cells in spleen. Liz-H regained the Cisplatin and Docetaxel–induced weight loss. Upregulation Muscle protein degradation gene (MURF-1, Atrogin-1) and decline of muscle synthesis gene (MyoD, Myogenin) after treatment of Cisplatin and Docetaxel were prevented by Liz-H. We also observed that administration of Liz-H recovered neutropenia and serum biochemistry in Cisplatin and Docetaxel-treated mice. This study indicated Ganoderma polysaccharides (Liz-H) could alleviate the Cisplatin and Docetaxel-induced side effects in lung cancer therapy.

並列關鍵字

Ganoderma polysaccharides ； Lung Cancer ； Cisplatin ； Docetaxel ； Side effets

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