Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposomes in vivo and in vitro

查看全文 作　　者：YongJin JunLi Long-FuRong Yuan-HaiLi LinGuo Shu-[1]YunXu

机构地区：[1]InstituteofClinicalPharmacology,SchoolofPharmacy,AnhuiMedicalUniversity,Hefei230032,AnhuiProvince,China

出　　处：《World Journal of Gastroenterology》索引2005年第11卷第17期,共4页

基　　金：Supported by the Key Teacher Foundation of Ministry of Education of China, No. 1869 Young Teacher Foundation of Department of Education of Anhui Province, No. 2000jp112 摘　　要：AIM: To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro.METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivoand in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay, In vivo experiment,the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry.RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100μmol/L) and free 5-Fu significantly inhibited HepA cell growth.Furthermore, IC50 of 5-Fu-GCL (34.5μmol/L) was lower than that of free 5-Fu (51.2μmol/L). In vivo experiment,5-Fu-GCL (20, 40, 80mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased.CONCLUSION: 5-Fu-GCL appears to have anti-hepato-carcinoma effects and its drug action is better than free 5-Fu. its mechanism is partly related to increased drug concentrations in intracallular fluid and liver tumor tissues,enhanced tumor cell apoptotic Fate and arrest of call cycle in S phase. 关键词：肝肿瘤 5-氟尿嘧啶胶囊制剂脂质体化学治疗

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Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposomes in vivo and in vitro

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