| Summary: | 碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 104 === Fatty acid synthase (FASN) is emerging as a new molecular targeted anti-cancer drug. In recent years, studies have shown FASN inhibition have notable effects on tumor cell growth and apoptosis in vitro and in vivo.
Liver cancer is a common malignant tumor, and the treatment is rather limited. But few studies discuss the fatty acid synthase inhibitor use in the treatment of liver cancer. So we want to observe the phenomenon after the treatment of FASN inhibitor in five different hepatoma cell line. And observing the metabolism of human hepatoma cell line. With the positron probe of [18F]FDG and [11C]acetate, attempting to obtain the observation of hepatoma cells and tumor accumulation. In addition to observe the effect of FASN-targeted therapy.
Hepatoma cell line SkHep1, PLC5, HepG2, Hep3B and Huh7 be explored in this study. First to understand the expression of fatty acid synthase and acetyl-CoA synthase 2 and the utilization of acetate. We found the expression of FASN and ACSS2, and the utilization of acetate are all associated with cell differentiation in different hepatoma cell lines. Tumors are situated in a metabolically challenging environment where blood supply, and the supply of oxygen and other nutrients that come with it, is scarce. We found that the expression of lipid metabolism gene will be upregulated.
Orlistat is a FASN inhibitor and be used in the study. Our data showed that Orlistat is worked by inhibit hepatoma cell to uptake acetate and the ability of fatty acid synthesis is be inhibited. In animal experiments, we found the tumor growth have been slowing in the treatment group.
In conclusion, this study demonstrate orlistat is a potential molecular targeted drug. Acetate and FDG PET tracers could provide an important biomarker for diagnosis and treatment response.
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