覆盆子抑制肺癌細胞之上皮間質轉化與其
移動及侵入之機制探討

葉加亨

doi:10.6834/CSMU.2011.00014

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覆盆子抑制肺癌细胞之上皮间质转化与其移动及侵入之机制探讨

Study of the inhibitory effects and its mechanisms of Rubus idaeus on Epithelial-Mesenchymal Transition, invasion and migration of lung cancer cells

叶加亨 , 硕士　　导师：谢易修;陈霈霓　　

繁体中文 DOI： 10.6834/CSMU.2011.00014

覆盆子；肺癌；侵袭；上皮间质转化； Rubus idaeus ； A549 ； lung cancer ； invasion ； migration

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摘要 │ 参考文献 (126) │ 国际计量

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The metastasis of cancer is a vital trait in malignance with extreme difficulties in early diagnosis and therapeutic management. Therefore, the development of new remedies or the utilization of natural medicines targeted at metastasis has been interested and studied extensively. Recently, Chinese medicinal herbs have been reported to have various anti-carcinogenesis properties, including inducing cell apoptosis and suppressing cell proliferation. However, the in vitro effect and detailed mechanism of Rubus idaeus on metastasis of cancer cells was still unclear. Hence, a highly metastatic human lung cancer cell line, A549, was chosen to be treated with Rubus idaeus extracts (RIE) to investigate their potential for inhibiting cancer cell migration and invasion. For a start, via wound healing assay and Boyden chamber assay, we found that RIE can suppress A549 cells migration and invasion, and RIE did not have toxicity to A549 cells by MTT assay. We also found that RIE can suppress A549 cells adhesion and cell spreading by cell adhesion assay. Based on that tumor metastasis are accompanied with proteolytic degradation of the extracellular matrix and changed cell motility. Both of MMP-2 and u-PA activity were also inhibited by RIE via gelatin zymography and casein zymography assay. We performed western blot analysis to find that RIE inhibited phosphorylation of FAK and Erk1/2. Furthermore, Treatment with RIE which was resulted in induction of epithelial markers such as E-cadherin and α-catenin and repression of mesenchymal markers such as Snail-1, vitmentin, fibronectin, and N-cadherin, which reduce cell invasion and metastasis. A treatment with RIE to A549 cells also suppressed the DNA binding activity and the nuclear level of activator protein-1. Finally, it was concluded that RIE may reverse Epithelial-Mesenchymal Transition and inhibit tumor cell metastasis via suppressing the expression of proteases, phosphorylation of Mitogen-activated protein kinase and the activity of transcription factors metastasis-related proteinase.

参考文献 ( 126 ) 〈TOP〉

Amir S, Margaryan NV, Odero-Marah V, Khalkhali-Ellis Z, Hendrix MJ (2005) Maspin regulates hypoxia-mediated stimulation of uPA/uPAR complex in invasive breast cancer cells. Cancer Biology & Therapy 4(4): 400-406
连结：
Andreasen PA, Georg B, Lund LR, Riccio A, Stacey SN (1990) Plasminogen activator inhibitors: hormonally regulated serpins. Molecular and Cellular Endocrinology 68(1): 1-19
连结：
Banyai L, Varadi A, Patthy L (1983) Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator. FEBS Letters 163(1): 37-41
连结：
Bernards R, Weinberg RA (2002) A progression puzzle. Nature 418(6900): 823
连结：
Cai KX, Tse LY, Leung C, Tam PK, Xu R, Sham MH (2008) Suppression of lung tumor growth and metastasis in mice by adeno-associated virus-mediated expression of vasostatin. Clinical Cancer Research 14(3): 939-949
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使用DOI作为永久连结

引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。