| Summary: | 碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 96 === 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. At present many kinds of Chinese medicinal herbs have the anti- inflammation, anti-allergic and anti-cancer activeness. Part of active principles had to be isolated and identified. 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 Chinese medicinal herbs on metastasis of cancer cells was still unclear. Hence, a highly metastatic human lung cancer cell line, A549, was chosen to be treated with viola yedoensison extracts (VYE) and phyllanthus urinaria extracts (PUE) to investigate their potential for inhibiting cancer cell invasion. For a start, via modified Boyden chamber invasion assay, we found that VYE and PUE can suppress A549 cells invasion. And this two Chinese medicinal herbs did not have toxicity to A549 cells. 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 VYE and PUE via gelatin zymography and casein zymography assay. We also found that VYE and PUE can suppress the expression of proteinase and change proteinase inhibitor expression through RT-PCR and Western blotting. Furthermore, VYE could decrease the phosphorylation of p38, as well as suppressed the DNA binding activity and the nuclear level of nuclear factor-kappa B (NF-(NF-kappaB) and PUE could also suppress the phosphorylation of JNK, Akt, the binding activity and nuclear level of activator protein-1 (AP-1). In addition, A549-bearing BALB/c mice and LLC-bearing C57BL/6 mice were treated with VYE and PUE which tumor weight monitoring throughout the experiment, finally tumor weight, and lung metastases of animals have decreased. Finally, it was concluded that VYE and PUE may inhibit tumor metastasis via suppressing phosphorylation of MAPKs or Akt, the activity of transcription factors metastasis-related proteinase and affecting their inhibitor.
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