Anti-proliferative Effect of S1P on Human Prostate Cancer PC-3 Cells

• Main Authors: Chung-Yi Huang, 黃仲億
• Other Authors: Yuan-Li Huang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/98444835871718060106

碩士 === 亞洲大學 === 生物科技學系 === 102 === Sphingosine 1-phosphate (S1P), a sphingolipid metabolites, regulates various cellular functions, such as cell proliferation and migration. Prostate cancer, the most common cancer in adult men, is relied on androgen and the 2nd-leading cause of cancer deaths in Western countries. Previous studies have shown that the S1P inhibited PC-3 cell growth, but the molecular mechanism remains unclear. In the present study, we investigated the possible signalling pathways involved in S1P-inhibited PC-3 cell survival. Through RNA interference (RNAi) analysis and chemical inhibitors, we showed that S1P1 binding with Gi protein is responsible for S1P-inhibited PC-3 cell survival. In addition, the MTT assay and western blot analysis, results showed that S1P inhibited phosphorylation of Akt via phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and SH2 domain containing inositol-5-phosphatase 2 (SHIP2) activation. Furthemore, the Akt phosphorylation regulated cyclin D1 and CDK4 to inhibit cell growth in PC-3 cells. Taken together, our results indicated that through binding to S1P1 and Gi protein, S1P activates PTEN and SHIP2 to suppress Akt phosphorylation and the downstream protein, cyclin D1 and CDK4 expression then inhibits PC-3 cell growth.