关键词: 一氧化氮合酶, 血管生成抑制剂, 内皮, 血管, 内皮生长因子, 血液

Abstract: 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.

Key words: nitric-oxide synthase, angiogenesis inhibitors, endothelium, vascular, endothelia growth factors, blood