摘要
目的研究诱导型一氧化氮合酶(iNOS)选择性抑制剂氨基胍(AG)对鼠胃癌MFC细胞增殖和凋亡的影响。方法将40只MFC胃癌皮下接种模型小鼠随机分成4组对照组(等体积生理盐水)、丝裂霉素组(MMC,每周注射2次,每次0.7mg/kg)、AG组(150mg·kg-1·d-1)和MMC加AG组。均采用腹腔内注射给药法,持续14d;停药后24h处死动物。应用Greiss反应法测定荷瘤动物血浆中一氧化氮(NO)量;剥离肿瘤,称重并计算抑瘤率;应用免疫组织化学法检测肿瘤细胞中增殖细胞核抗原(PCNA)的表达,TdT介导的dUTP缺口末端标记(TUNEL)法检测肿瘤细胞的凋亡,透射电镜观察凋亡细胞的超微结构。结果AG显著降低荷瘤小鼠血浆中NO的合成,明显抑制肿瘤的生长,抑瘤率为47.1%,与对照组比较,P<0.01。AG组的肿瘤细胞PCNA表达值为25.2±3.6,MMC加AG组为22.0±3.6,明显低于对照组的82.0±3.6(P<0.01);但凋亡指数未见下降,电镜下亦未见典型的细胞凋亡形态学变化。结论AG通过抑制肿瘤组织中NO的产生而抑制肿瘤生长,但并未促进肿瘤细胞凋亡。
Objective To investigate the effects of aminoguanidine (AG),a selective inhibitor of inducible nitric oxide synthase on proliferation and apoptosis of MFC stomach cancer in mice. Methods The mice stomach carcinoma cell line MFC was implanted subcutaneously in kunming mice. Mice were randomly divided into 4 groups: control group (saline solution),MMC group (mitomycin,twice a week 0.7 mg/kg ),AG group (AG,150 mg·kg-1·d-1) and combined treatment of both MMC and AG group. All drugs were given by intraperitoneal injection. The mice were sacrificed after 2 weeks and the tumors were processed for histological examination. In addition,sera were collected and nitrite levels were tested using Greiss assay. The expression of proliferating cell nuclear antigen (PCNA) in tumors was detected by immunohistochemical method and apoptosis in tumors was measured by TdT mediated biotinyated dUTP nick end labeling (TUNEL) method. The ultrastructural features of apoptosis cells were observed under electromicroscope. Results Compared with the negative control group,the growth of the orthotopically implanted tumor was significantly inhibited by AG and the inhibitory rate was 47.1%. Expression of PCNA in AG treated group was lower than that in the control group,but no significant difference in apoptosis index (AI) was found. Typical morphological changes of apoptosis in tumor cells were not observed in AG treated group. Conclusion AG can significantly inhibit tumor growth by inhibiting the production of NO,but can not promote the apoptosis of MFC cells.
出处
《中华胃肠外科杂志》
CAS
2004年第6期496-498,共3页
Chinese Journal of Gastrointestinal Surgery
基金
吉林省自然科学发展基金资助项目(20010536)
