齐墩果酸多囊脂质体用于肝癌治疗的初步研究

发布时间：2018-10-20 18:46

【摘要】：目的:将多囊脂质体(MVLs)用于包载齐墩果酸(OA),制备一种新型给药系统齐墩果酸多囊脂质体(OA-MVLs),克服OA的难溶性缺点,延长药物的消除时间,并初步验证OA-MVLs对正常人肝细胞L-02、人肝癌细胞HepG2和SMMC-7721细胞的抑制作用;拟考察利用最佳处方制备的OA-MVLs能否抑制肝癌细胞的迁移、侵袭,能否抑制肿瘤增长,降低毒副作用。方法:本研究采用已获得的最优处方制备OA-MVLs后,以肝癌细胞SMMC-7721和HepG2为细胞模型,分别给予不同剂量的OA-MVLs和OA,对细胞的活力、黏附、迁移和侵袭能力进行评价。随后,通过大鼠体内毒性实验对OA-MVLs的毒副作用进行考察。最后,构建H22荷瘤小鼠模型,对OA-MVLs的抗肿瘤活性进行检测。结果:实验结果表明,OA-MVLs能显著降低体外肝癌细胞的活力、黏附、迁移和侵袭。此外,当浓度为160μmol/L时OA-MVLs对肝癌细胞有抑制作用,但是对正常肝细胞却无影响。体内毒性实验表明,低、中剂量的OA-MVLs对实验大鼠无毒副作用。OA-MVLs能抑制H22荷瘤小鼠肿瘤的生长并且延长其生存时间。结论:OA-MVLs能抑制体外肝癌细胞的生长、黏附、迁移和侵袭,具有抗肿瘤活性,能抑制肿瘤的生长,低、中剂量的OA-MVLs更适用于肝癌治疗的剂量选择。
[Abstract]:Objective: to prepare a new delivery system of oleanolic acid polythylated liposome (OA-MVLs) by using polythylated liposome (MVLs) for encapsulating oleanolic acid (OA),. The inhibitory effects of OA-MVLs on normal human hepatocytes L-02, HepG2 and SMMC-7721 cells were preliminarily tested, and whether the OA-MVLs prepared with the best prescription could inhibit the migration, invasion, tumor growth and toxicity of hepatoma cells. Methods: in this study, OA-MVLs was prepared with the best prescription. The cell models of SMMC-7721 and HepG2 were used to evaluate the viability, adhesion, migration and invasion of hepatoma cells by different doses of OA-MVLs and OA, respectively. Then, the toxicity and side effects of OA-MVLs were investigated in vivo. Finally, the anti-tumor activity of OA-MVLs was detected by constructing H 22 tumor-bearing mice model. Results: the results showed that OA-MVLs could significantly reduce the viability, adhesion, migration and invasion of hepatoma cells in vitro. In addition, at the concentration of 160 渭 mol/L, OA-MVLs inhibited hepatoma cells, but had no effect on normal hepatocytes. In vivo toxicity test showed that low and middle dose of OA-MVLs had no side effects on experimental rats. OA-MVLs could inhibit tumor growth and prolong survival time of H22 tumor-bearing mice. Conclusion: OA-MVLs can inhibit the growth, adhesion, migration and invasion of hepatoma cells in vitro. It has anti-tumor activity and can inhibit tumor growth. Low dose OA-MVLs is more suitable for the treatment of liver cancer.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.7

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