| Summary: | 碩士 === 嘉南藥理科技大學 === 生物科技系暨研究所 === 99 === Tomatidine, isolated from tomato, is a naturally occurring steroidal glycoalkaloid. Recent study demonstrated that tomatidine suppressed inflammation by reducing iNOS and COX expression. However, the effect of tomatidine on metastasis of caner cell is still unclear. In the present study, we aimed to elucidate the potential of tomatidine on suppressing migration and invasion of human lung cancer cell A549. We found that treatment of 50 μM of tomatidine for 24 and 48 h could inhibit A549 cell proliferation. The nontoxic doses of tomatidine were utilized to examine its anti-migratory and anti-invasive activities by in vitro wound healing assay and Boyden chamber invasion assay, respectively. We demonstrated that the cells migration was not altered significantly, whereas cell invasion was suppressed markedly. The inhibitory mechanisms of tomatidine associated with anti-invasion were investigated further. Tomatidine reduced the activity and expression of matrix metalloproteinase-2 and MMP-9 (MMP-2 and MMP-9) which are involved in cell invasion. Meanwhile, tomatidine can significantly suppressed the upstream signaling of MMP-2 and MMP-9 including PI3K, Akt and MAPK pathways. Taken together, these results suggested that tomatidine inhibited A549 invasion by reducing MMP-2 and MMP-9 activity and these findings reveal a new therapeutic potential for tomatidine on anti-metastatic therapy.
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