氨基胍对小鼠移植性胃癌的影响

Effects of aminoguanidine on transplantation stomach cancer in mice

目的 :研究诱导型一氧化氮合酶 (i NOS)选择性抑制剂氨基胍 (AG)对皮下接种 MFC胃癌细胞株小鼠的抑瘤作用 ,探讨其抑瘤机制。方法 :5 0只皮下接种 MFC胃癌细胞株小鼠动物模型 ,随机分为 5组。接种后 2 4 h开始 ,分别给予生理盐水 (阴性对照组 )、丝裂霉素组 (每周注射 2次 ,每次 0 .7mg· kg- 1 ,MMC组 )、小剂量 AG组 (5 0 mg· kg- 1 · d- 1 ,AGL 组 )、大剂量 AG组 (1 5 0 m g· kg- 1 · d- 1 ,AGH组 )、丝裂霉素与 AG联合给药组 (MMC每周注射 2次 ,每次 0 .7mg· kg- 1 ,AGH1 5 0 mg· kg- 1· d- 1 ,MMC+AGH 组 )。均采用腹腔内注射 ,2周后处死动物剥离肿瘤 ,称重并计算抑瘤率 ;应用 Greiss反应法测定荷瘤动物血浆中 NO含量 ;HE和免疫组化 (SP法 )染色 ,分别计数微血管密度 (MVD)、 i NOS和血管内皮生长因子 (VEGF)阳性率 ,分析它们与AG抑瘤效应之间的关系。结果 :联合用药组抑瘤率为 5 2 .9% ,AGH 组为 4 7.1 %。联合用药组 MVD为 (8.8± 2 .6 ) % ,AGH 组为 (2 1 .2± 1 2 .4 ) % ,显著低于对照组 (P<0 .0 1 )。联合用药组 VEGF阳性率为 (2 .1±1 .4 ) % ,AGH 组为 (4 .8± 1 .6 ) % ,同对照组比较差异有显著性 (P<0 .0 1 )。联合用药组 i NOS阳性率为 (2 .4±1 .1 ) % ,AGH 组为 (3.8± 0 .9)

Objective To investigate the inhibitory effects of aminoguanidine(AG),a selective inhibitor of inducible nitric oxide synthase(iNOS), on mice stomach cancer and its′mechanism. Methods The mice stomach cancer cell lines MFC were implanted subcutaneously in Kunming mice.Fifty mice were randomly divided into 5 groups: Control group (saline solution), MMC group (Mitomycin, twice a week 0 7 mg·kg -1 i p ),low dosage AG group (AG L, 50 mg·kg -1 ·d -1 i p ), high dosage AG group (AG H, 150 mg·kg -1 ·d -1 i p ) and combined treatment of both MMC and high dosage AG group(MMC+AG H).All drugs were given by intraperitoneal injection. Two weeks after implantation, the mice were sacrificed, and the tumor weight,inhibitory rates,intratumoral microvessel density (MVD),the positive rate of vascular endothelial growth factor (VEGF) and iNOS were evaluated,respectively. In addition,serum were collected and nitrite levels were tested using Greiss assay. Results Compared with the negative control group,the growth of the orthotopically implanted tumor was significantly inhibited due to the reduced weight and the inhibitory rates of tumor in AG H group and MMC+AG H group were 47 1% and 52 9%,respectively. The MVD was decreased significantly in MMC+AG H group and AG H group [(21 2±12 4)% and (8 8±2 6)%],compared with control group [(68 3±10 6)%] ( P <0 01). The positive rates of VEGF and iNOS in negative control group were (10 3±1 6)% and (11 3±1 3)%. However,they were (4 8±1 6)%,(3 8±0 9)% and (2 1±1 4)%,(2 4±1 1)% in AG H group and MMC+AG H group,respectively.Conclusion AG can significantly restrain the development of mice stomach cancer through inhibiting the expression of iNOS,VEGF and decreasing MVD. Combination treatment can improve the inhibitory effect.