探討牛樟芝CCM111對細胞訊息傳遞之影響

牛樟芝，是台灣菌類特有種。一直以來被台灣原住民作為解酒以及治療肝病的中草藥。有研究報導指出，牛樟芝萃取物具有抗肝炎病毒的效果並且能夠抑制肝癌的形成。在我們先前的實驗中得知，牛樟芝的確具有抗腫瘤生長的功能，並且若是同時給予牛樟芝與化療藥物則更能增加抗腫瘤的效果。訊息傳遞控制了細胞的功能，如細胞增生、分化等。而我們知道，許多癌症的產生與訊息傳遞的異常表現有關係。因此欲建立訊息傳遞平台，進行對牛樟芝的全面性篩選，進而得知牛樟芝能透過調控哪一條訊息傳遞而達到抗發炎反應甚至抗腫瘤生長的功能，為我實驗的主要目的。經過一連串的冷光訊息傳遞細胞株測試，牛樟芝萃取物CCM111對調控發炎反應的STAT3訊息傳導路徑具有顯著的抑制效果。在蛋白質層面也可以發現CCM111抑制了STAT3 蛋白質的磷酸化表現。除此之外，中草藥的多重成分也會影響其他訊息傳遞路徑，如MAPK/JNK和Wnt皆受到CCM111的調控。針對CCM111測試巨噬細胞的發炎反應以及小鼠肝纖維化情形，得知CCM111可以有效的抑制發炎反應的產生同時也能抑制小鼠肝纖維化的情形。此研究完成了牛樟芝對各訊息傳遞的初步影響。並且在針對牛樟芝對STAT3訊息傳遞的影響作更進一步的探討後，得知CCM111可以降低STAT3蛋白質在Tyr705的磷酸化程度。而STAT3是和發炎反應相關的訊息傳遞，此結果也和巨噬細胞及動物實驗的結果一致。未來希望能研究CCM111對STAT3在癌症細胞上的影響為何。

關鍵字

發炎反應；中草藥；牛樟芝；訊息傳遞

並列摘要

CCM111, an extraction of Antrodia camphorate (AC) is a genus of fungi in Taiwan. It is well known as a Traditional Chinese Medicine (TCM) and has been widely used during Taiwanese aborigines as a drug for treating hangover and liver diseases. Previous data in our laboratory showed that AC may enhance the therapeutic function with chemotherapy drugs. The signaling transduction pathways control the cell biological mechanism such as cell proliferation and apoptosis. In my study, we have collected 14 stable cell lines expressing transcriptional regulatory elements in front of luciferase reporter to monitor activity of the signaling pathways. To understand the effect of CCM111 in different signaling pathways, we performed a serial of luciferase reporter experiments to dissect the mechanism of CCM111. After a serial luciferase reporter experiment, CCM111 shows significantly inhibition effect in STAT3 signaling pathway. STAT3 pathway is involved in inflammation effect. We also found CCM111 decrease the phosphorylation level of STAT3 protein. Furthermore, MAPK/JNK and Wnt pathways were inhibited by CCM111. In addition, macrophage cells were tested with CCM111 on expression level of iNOS and COX2 and the level of liver fibrosis in mice. The preliminary results have shown that CCM111 trigger anti-inflammation effects. The expression of CCM111 in cancer cell lines will be our next step in this study.

並列關鍵字

inflammation ； signaling transduction pathway ； Antrodia camphorate ； Traditional chinese medicine

參考文獻

1. Ao, Z.H., et al., Niuchangchih (Antrodia camphorata) and its potential in treating liver diseases. J Ethnopharmacol, 2009. 121(2): p. 194-212.

2. Phuong do, T., et al., Inhibitory effects of antrodins A-E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease. Phytother Res, 2009. 23(4): p. 582-4.

3. Corvinus, F.M., et al., Persistent STAT3 activation in colon cancer is associated with enhanced cell proliferation and tumor growth. Neoplasia, 2005. 7(6): p. 545-55.

4. Levy, D.E. and C.-k. Lee, What does Stat3 do? J Clin Invest, 2002. 109(9): p. 1143-1148.

5. Scheidereit, C., IκB kinase complexes: gateways to NF-κB activation and transcription. Oncogene, 2006. 25(51): p. 6685-6705.

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探討牛樟芝CCM111對細胞訊息傳遞之影響

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