Cerulenin Inhibits Growth Of Human Osteosarcoma (U2-OS) In Nude Mice

Objective: To invetisget the inhibitory effect of Fatty Acid Synthase inhibitor , cerulenin , on the growth of transplanted tumors of human osteosarcoma(U2-OS) in nude mice.Methods: U2-OS human osteosarcoma xenografts were used as preclinical tumor models. The nude mice(18)bearing U2-OS human osteosarcoma were divided randomly into three groups.DMSO solution,40mg/kg Cerulenin and 80 mg/kg Cerulenin were intraperitoneal injected separately every other day for 6 times. After 18 days, the mice were killed .The weigh and volumn of the tumor were measured ,while their inhibition ratio were evaluated. Histopathological changes of the tumors were observed. TUNEL apoptosis assay kit to examine U2-OS cell's apoptosis.Result: Both the weight and volume of the tumor in two cerulenin treated groups were decreased .The weight inhibited ratio was 49.1% in low dose cerulenin treated group,while 25.5% in the high.The volumn inhibited ratio was 52.1% and 24.2% differently between two treated groups.The data were all significantly different among the three groups( P<0.05). The histopathological features showed that death of U2-OS cells treated by cerulenin was associated with apoptosis characterized by disappeared cell microvillus and hign density cytoplasm. High dose cerulenin induced 17.1% apoptosis,while the low induced 10.3%, both much highed than the data 3.5% in control group. Apoptotic index were significantly different among the three groups( P < 0.05) .Conclusion: Cerulenin can effectively inhibit the growth of human osteosarcoma(U2-OS)cells in vivo. The mechanism of cell death may be correlated with apoptosis .