| Summary: | 碩士 === 中山醫學大學 === 口腔材料科學研究所 === 101 === Initiation, growth, recurrence, and metastasis of oral cancer have been relative to cancer stem cells, which exhibit self-renewing capacity and responsible for tumor maintenance. Oral cancer stem cells (OC-SCs) are cell with high level aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. Targeting cancer stem cells would be a new strategy to improve the treatments for oral cancer-related malignancies. Silibinin(SB), a polyphenolic flavonoid compound isolated from milk thistle seed extracts, is one of natural agents that have been shown to have biological efficacy in against a variety of cancers. Until now, the effect of SB in targeting oral cancer stem cells remains unknown.
We first observed that SB inhibited growth of OC-SCs, but there was no cytotoxicity on normal oral cells. In addition, SB down-regulated the ALDH1 activity, self-renewal property, cell invasion, and chemo-resistance of sphere-forming OC-SCs. Importantly, an in vivo nude mice model showed that SB treatment reduces the growth of xenograft tumors by oral gavage. Above all, SB would be a potential targeted therapy for OC-SCs. MicroRNAs (miRNAs) — highly conserved small RNA molecules that regulate gene expression — can act as cancer signatures, and as oncogenes or tumor suppressors depending on its main target genes. Using miRNAs microarray and Real-time PCR, our study found SB increased microRNA-494 expression in OC-SCs. Clinically, compared with non-tumor samples from oral cancer patients, the expression levels of microRNA-494 were decreased in all of the tumor samples. microRNA-494 could be biomarker of oral cancer patients.
In conclusion, SB would be a potential natural agent on targeting OC-SCs by up-regulation of miR-494.
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