Lovastatin inhibits stemness genes and invasion of oral cancer stem cells

• Main Authors: Chi-Yu Hong, 洪志瑜
• Other Authors: YEN-PING KUO
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/qbj4w4

碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 107 === According to the 106-year cancer registration report released by the Ministry of Health and Welfare, oral cancer is the fifth leading cause of death among men in Taiwan . Despite the improvement in the diagnosis and treatment of oral cancer in recent years, the five-year survival rate of patients has not improved significantly. Treatment failure and recurrence are attributed to cancer stem cells. Cancer stem cells, a small part of cancer cells, are highly tumorigenic cancer cells that are capable of self-renewal and asymmetric division leads to differentiation into various heterogeneous cancer cells to cause tumor formation. It is worth noting that recent studies have shown that cancer stem cells are resistant to conventional treatment and drive local recurrence and metastasis. Since cancer stem cells would highly express embryonic stem cell proteins, if we can effectively inhibit these specific proteins, we would eliminate the resistance of cancer stem cells to chemical drugs and radiation therapy. Lovastatin, the HMG-CoA reductase inhibitors, not only lower serum cholesterol but also have antitumor effects in many cancer cell such as colorectal cancer, head and neck cancer, breast cancer and lung cancer in recent years. Professor Kuo’s lab has previously successfully cultured oral cancer stem cells in a sphere form from oral cancer cell lines. This study explores the potential of lovastatin for suppressing oral cancer stem cells in the future. First, we treat SAS cell line with different concentrations of lovastatin, MTT results found that the concentration of 1~5M does not affect the cell viability of SAS sp (IC50=10M), and lovastatin at a concentration of 1~50 M does not affect the cell viability of normal fibroblasts; then in the sphere forming assay, the higher the concentration of lovastatin, the formation of sphere number and size decreased; in the invasion assay, 5 M lovastatin almost completely inhibited the invasion of SAS sp, and we further treated SAS sp with lovastatin and zoledronic acid(FPP synthase inhibitor), using qPCR and western blotting we found that 5M lovastatin and 2.5M zoledronic acid inhibit the expression of stemness-associated genes such as OCT4, SOX2 and KLF4. Lovastatin have the potential to inhibit oral cancer stem cell by inhibiting the geranylgeranylation of Ras oncogene.