ABSTRACT
Background : Fatty acid synthase (FASN) is overexpressed in a variety of human cancers, and may be involved in cancer metastasis. Hence, the strategies targeted on FASN may have therapeutic potential for treating cancer metastasis. Objectives : The aim of this study is to investigate the correlation of FASN expression with metastasis in human osteosarcoma. Materials and Methods : Human osteosarcoma cell lines U2-OS and osteosarcoma biopsy specimens were employed in this study. The expression of FASN protein in osteosarcoma specimens was detected by IHC (immunohistochemistry) and the relationship with metastasis was analyzed. We performed the cerulenin, an inhibitor of FASN, to inhibit FASN expression in U2-OS cells. Western blot and RT-PCR were performed to investigate the expression of FASN in U2-OS cells. Cells mobility was detected by wound healing and Transwell assays. Results : Results showed that the FASN expression level in the cases with pulmonary metastases was significantly higher than in those without metastasis. In vitro, the invasion and migration of U2-OS cells were suppressed by inhibiting FASN. Our findings suggested that FASN may be involved in osteosarcoma metastasis
Subject(s)
Adolescent , Antineoplastic Agents/pharmacology , Blotting, Western , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cerulenin/pharmacology , Child , Child, Preschool , Enzyme Inhibitors/pharmacology , Fatty Acid Synthase, Type I/antagonists & inhibitors , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Male , Osteosarcoma/pathology , Osteosarcoma/secondary , Real-Time Polymerase Chain ReactionABSTRACT
Ergosterol was observed to alter the lipid composition of C. albicans 3153 selectively, resulting in steep rise in ergosterol content with marginal changes in other lipids content. Supplementation of ergosterol in presence or absence of cerulenin made cells more protective towards the miconazole drug. However, when the same experiments were carried out with liposomes prepared from the lipid extracts of control and supplemented cells, the pattern obtained show a little deviation from the in vivo experiments thus indicating that in addition to lipids, other cell components like proteins also affect interaction of miconazole with C. albicans.
Subject(s)
Candida albicans/drug effects , Cerulenin/pharmacology , Ergosterol/pharmacology , Lipid Metabolism , Miconazole/pharmacologyABSTRACT
Cerulenin, a specific inhibitor of fatty acid and sterol biosyntheses, inhibited growth and lipid synthesis in C. albicans, which on supplementing the growth medium with optimum concentrations of fatty acids was reversed. Significant changes in the levels of phospholipids and sterols were observed in fatty acid-supplemented cells. Altered phospholipids and their fatty acid profile rendered cells more resistant to miconazole and thereby more permeable to [3H]proline. Thus it appears that fatty acid composition plays an important role in determining the permeability susceptibility of C. albicans to drugs.