| Summary: | 碩士 === 中國醫藥大學 === 中國藥學暨中藥資源學系碩士班 === 99 === According to the statistic analysis the most common death cause is cancer. Metastasis in cancer patients is often fatal cancer caused by one of the reasons. Inotilone is a major component from Phellinus Linteus, one of the traditional Chinese medical herbs, which have been proved to have such effects as anti-oxidation and anti-inflammation. However, the mechanism of inotilone on the anti-metastasis is still unclear.
In this study, inotilone was used to evaluate growth inhibition, the inhibitory effects of inotilone on the growth of tumor cells were determined by MTT assay. Inotilone showed a inhibit effect on cell migration and invasion by transwell chamber assay. In addition, we found that inotilone can reduce the MMP-2, MMP-9 and uPA activity by gelatin and casein-plasminogen zymography. Western blot analysis is then to confer the inhibition of the MMP secretion and the promotion of TIMP secretion. Inotilone in A549 cell inhibited cancer metastasis pathway may reduce the protein expressions of inflammation-related such as iNOS and COX-2…etc, and inhibit the MAPK and WNT pathway.
In addition, the ability of inotilone in inhibition of cancer metastasis can also be seen in animal experiments. C57BL6 mice were implanted subcutaneously with LLC cells and three days later determined the tumor was induced successful then start to give inotilone as treatment. After sacrificing the animals, it was found that inotilone not only reduced the activity of MMP-2 and MMP-9, but also inhibited TNF-α activity and reduced NO content. In LLC-bearing mice, inotilone reduced the MMP-9 and increased the TIMP-2 protein expression in lung tissues and the antioxidant enzymes in lung tissues such as catalase, SOD and GPx activity was improved. So the results also confirm that the anti-metastatic efficacy of inotilone may be related to the antioxidant activities.
The results indicated that inotilone exerted anti-metastatic efficacy associated with not only MAPK and WNT signaling pathways but also related to inflammation-related factors and antioxidant activities.
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