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

陳佩君

doi:10.6845/NCHU.2015.01019

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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

陳佩君 , Masters　　Advisor：胡淼琳　　Co-advisor ：喬長誠

繁體中文 DOI： 10.6845/NCHU.2015.01019

樟芝菌絲體醣蛋白；癌轉移；順鉑；小鼠肺癌細胞； Antrodan ； Metastasis ； Cisplatin ； Lewis Lung carcinoma

Abstract │ Reference (49) │ Altmetrics

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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.

Reference ( 49 ) 〈TOP〉

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