| Summary: | 博士 === 中山醫學大學 === 醫學研究所 === 104 === Glioblastoma multiforme (GBM) is a severely invasive tumor that can be fatal because it is difficult to treat. Tricetin, a natural flavonoid, was demonstrated to inhibit the growth of various cancers, but the effect of tricetin on cancer motility is largely unknown. In the present study, we examined the anti-invasive properties of tricetin in human GBM cells. Our results showed that tricetin (20-80 µM) inhibited the migration/invasion of two GBM cell lines (GBM 8401 and U87). During cancer metastasis, the extracellular matrix (ECM) was decomposed by releasing of growth factors and matrix metalloproteinases (MMPs), followed by angiogenesis formation through the blood flow, and then transferring to other organs. We found that tricetin inhibited matrix metalloproteinase (MMP)-2 expression in the GBM cells. Real-time PCR and promoter activity assays indicated that tricetin inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of specificity protein 1 (SP-1) DNA-binding activity and SP-1 expression. An examination of clinical samples revealed a positive correlation between SP-1 and MMP-2 in glioma specimens, and higher expression levels were correlated with a
worse probability of survival. Moreover, blocking the ERK pathway also inhibited MMP-2-mediated cell motility, and further enhanced the anti-invasive ability of tricetin in GBM 8401 cells. In conclusion, SP-1 is an important target of tricetin for suppressing MMP-2-mediated cell motility in GBM cells, and a combination of tricetin and an ERK inhibitor may be a good strategy for preventing GBM invasion.
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