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標題: 樟芝菌絲體醣蛋白Antrodan合併順鉑在小鼠異體移植肺癌細胞株(LLC1)之模式中抑制腫瘤轉移並改善順鉑的腎毒性
Antrodan, a glycoprotein isolated from Antrodia cinnamomea mycelia, in combination with cisplatin inhibits tumor metastasis and protects against cisplatin-induced nephrotoxicity in C57BL/6 mice xenografted with Lewis lung carcinoma
作者: 陳佩君
Pei-Chun Chen
關鍵字: Antrodan
Lewis Lung carcinoma
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摘要: Antrodia cinnamomea is a species known to be a treasured medicinal mushroom in Taiwan. Several studies have indicated that Antrodan, the glycoprotein from Antrodia cinnamomea mycelia, exhibits anti-inflammation and anti-oxidative actions. In addition, Antrodan has been shown to inhibit cancer metastasis in Lewis lung carcinoma (LLC) through direct action and immunomodulation. However, it is still unclear whether Antrodan has anti-metastatic effects in vivo. This study aimed to investigate the anti-metastatic effects of Antrodan and Antrodan in combination with cisplatin and to explore the protective effects of Antrodan against cisplatin-induced nephrotoxicity using tumor xenografted mice. LLC were injected (s.c.) into to C57BL/6 mice for 9 days, and mice were administered with Antrodan (20 and 40 mg/kg; p.o.) daily, cisplatin (1 mg/kg; i.p.) twice per week or their combined treatment for an additional 28 days. Results reveal that Antrodan treatment significantly (1) inhibited the number of tumor metastasis in lung and liver tissues and primary tumor growth; (2) decreased activities of urokinase-type plasminogen activator, matrix metalloproteinase (MMP)-2 and -9 in plasma; (3) reduced MMP-2/9 protein expression of and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK), including extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK) and p38 in lung and liver tissues; (4) decreased plasma interleukin-6 level and increased interferon-γ level. Cisplatin exhibited similar inhibitory effects, except for the number of tumor metastasis in lung tissues. The combined treatment exhibited additive action on inhibition of primary tumor growth, plasma MMP-9 activity, and protein expression of MMP-2 and MMP-9 in lung and liver tissues. In addition, Antrodan effectively improved cisplatin-induced nephtotoxicity, as evidenced by decreased cisplatin-induced blood urea nitrogen levels in plasma and p38 phosphorylation in kidney. Overall, the present results demonstrate that Antrodan has abilities to inhibit cancer metastasis and to improve nephrotoxicity induced by cisplatin in vivo.
牛樟芝為台灣特有的藥用菇蕈類。研究指出,樟芝菌絲體醣蛋白(Antrodan)具有抗發炎及抗氧化作用,此外,Antrodan已被證明在小鼠肺癌細胞(Lewis Lung carcinoma, LLC)中,可經由直接與免疫調節的作用抑制癌細胞轉移;然而,Antrodan在活體內是否具有抗癌轉移效果,目前仍不清楚。因此本研究利用腫瘤異體移植小鼠模式探討Antrodan與抗癌藥物順鉑(cisplatin)合併使用是否可減少cisplatin所造成的腎毒性。將LLC細胞以皮下注射方式接種入C57BL/6小鼠的背部,於癌細胞注射九天後,小鼠以管餵方式每日給予Antrodan (20及40 mg/kg)並以每周兩次的頻率以腹腔注射給予cisplatin (1 mg/kg),持續28天。結果顯示,Antrodan可顯著地(1) 抑制肺臟與肝臟腫瘤轉移數量及原位腫瘤生長;(2) 降低血漿中尿激酶型血纖維蛋白溶解酶原活化因子(urokinase-type plasminogen activator, uPA)與基質金屬蛋白酶(matrix metalloproteinases, MMPs)-2與-9的酵素活性;(3) 降低肺臟及肝臟中信號轉導及轉錄激活蛋白3 (signal transducer and activator of transcription 3, STAT3)、降低有絲分裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)包括细胞外調節蛋白激酶 (extracellular regulated protein kinases, ERK)、c-Jun氨基末端激酶(c-Jun N-terminal kinase, JNK)及p38之磷酸化作用與MMP-2及MMP-9的蛋白質表現;(4) 減少血獎中介白素-6含量及增加血漿中IFN-γ含量。而cisplatin也具有類似抑制效果,除了無法抑制肺臟腫瘤轉移數目外。此外,於Antrodan改善cisplatin造成的腎毒性部分,Antrodan可有效減少小鼠血漿中尿素氮含量及降低腎臟中p38磷酸化作用。綜合以上結果,本研究證明Antrodan在活體內具有抑制腫瘤轉移的能力並改善cisplatin所造成的腎毒性。
文章公開時間: 2015-08-25
Appears in Collections:食品暨應用生物科技學系



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