摘要
目的 观察氨基葡萄糖盐酸盐(GlcNH2·HCl)、氨基葡萄糖(GlcNH2)和N-乙酰氨基葡萄糖(NAG)体外抑制人肝癌细胞(SMMC-7721)生长的作用,对小鼠S18。肉瘤的肿瘤抑制作用以及对免疫系统的影响并探讨其作用机制。方法 采用MTT法检测不同浓度的单糖对SMMC-7721细胞生长的影响,倒置显微镜观察细胞形态,琼脂糖凝胶电泳进行DNA断裂分析,流式细胞仪检测对细胞周期的影响。采取灌胃给药的方式,观察GlcNH2·HCl对S18。小鼠瘤重、胸腺重和脾重以及荷瘤小鼠淋巴细胞转化率的影响。结果 GlcNH2·HCl和GlcNH2能明显抑制肝癌细胞SMMC-7721的生长,且存在剂量依赖性,在500μg·mL^-1浓度下,Glc-NH2·HCl和GlcNH2的抑制率为50.24%和52.19%,在1000μg·mL^-1浓度下的抑制率分另0为82.21%和83.2%。GlcNH2·HCl对SMMC-7721细胞存在周期特异性,可以使细胞发生S期阻滞。NAG对肝癌细胞的生长没有明显抑制作用。GlcNH2·HCl在125~500mg·kg^-1的剂量范围内,对小鼠S180肉瘤均有一定的抑制作用,平均抑瘤率在27.84%~34.02%之间,其中250mg·kg^-1剂量的抑制作用最强,在该剂量范围下,GlcNH2·HCl对荷瘤小鼠具有明显增加胸腺指数和脾指数的作用,同时促进荷瘤小鼠脾脏T淋巴细胞转化,无明显毒副作用。结论 GlcNH2·HCl体外呈剂量依赖性抑制人肝癌细胞SMMC-7721的生长,体内可能是通过直接杀伤肿瘤细胞的细胞毒作用和提高S180肉瘤小鼠细胞免疫水平来发挥抑瘤作用。
Objective The growth inhibitory effects of GlcNH2 · HCl, GlcNH2 and NAG on human hepatoma SMMC-7721 cells in vitro was investigated. The antitumor activity of GlcNH2 · HCl against Sarcoma180 in KM mice was also investigated. Methods The cell viability in vitro was examined with MTT assay. DNA isolation and cell-cycle analyses were also performed. GlcNH2 · HCl was ig administered to Sarcoma180 KM mice. The inhibition rates, spleen and thymus index were calculated. Results GlcNH2 · HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth. The inhibition rates against SMMC-7721 cell of GlcNH2 · HCl and GlcNH2 at concentration of 500μg·mL^-1 were 50.24% and 52. 19%. As to the concentration of 1000μg·mL^-1, the rates were 82.21% and 83.20% . This effect was accompanied by a marked increase in the proportion of S phase cells. Compared with the control, there was no significant difference among various concentrations of NAG, GlcNH2 · HC1 exhibited inhibitiory effect against Sarcomas80 in mice at the dosage of 125~500 mg ~ kg^-1 , and the inhibition rate was about 27.84%~34. 02%. The optimal inhibitory effect was 250 mg ~ kg^-1. GlcNH2 ~ HCl could enhance the weights of thymus and spleen. In addition, it could promote lymphocyte transformation. Conclusion It is therefore postulated that the antitumor effect of GlcNH2 - HC1 is probably host-mediated and cytocidal.
出处
《中国海洋药物》
CAS
CSCD
2006年第2期26-31,共6页
Chinese Journal of Marine Drugs
基金
国家"十五"863课题资助项目(2001AA625050)