【作者】 于丽波； 董新舒； 孙文洲； 徐海涛；

【Author】 Yu Li-Bo Dong Xin-Sbu Sun Wen-Zhou Xu Hai-Tao Department of General Surgery, Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China

【机构】 哈尔滨医科大学附属第三医院腹外科；

【摘要】 目的:观察一氧化氮合酶抑制剂N-硝基精氨酸甲酯(L—NAME)对人大肠癌细胞(LS1747T)皮下裸鼠移植瘤生长的影响,并探讨其抑制肿瘤的相关机制。方法:建立裸鼠皮下移植瘤模型,随机分为4组,每组6只。对照组:灌胃0． 2ml／次生理盐水,L—NAME组:L—NAME1．5mg／kg灌胃, 5-Fu组:5-Fu 5mg／kg灌胃,L-NAME+5-Fu联合组: L-NAME1．5mg／kg+5-Fu5mg／kg灌胃。3次／周,共二周,每周记录肿瘤大小,实验结束后,断颈处死裸鼠。解剖后完整剥出肿瘤组织,称瘤重并计算抑瘤率。采用免疫组化法、Western blot方法检测L-NAME组肿瘤组织MVD、 VEGF蛋白表达的影响。结果:在裸鼠体重方面:各组间鼠重无显著性差异,与实验前相比体重改变也不明显。在瘤重方面:各治疗组与对照组比较差异显著(P<0．01),联合治疗组与L-NAME组、5-Fu组相比,差异也有显著性(P <0．01)。在肿瘤体积方面:各治疗组与对照组比较,差异有显著性(P<0．01),联合治疗组与L-NAME组、5-Fu组比较,差异也有显著性(P<0．01),Q等于1．163,说明L- NAME和5-Fu联合用药具有协同作用,显著提高了5-Fu的抑瘤作用。肿瘤组织新生血管内皮细胞被染成棕黄色,癌组织内微血管形态不规则,部分血管无明显管腔,表现为内皮细胞簇,新生血管可分布在肿瘤任何位置。MVD值对照组为 28．94+2．67,L-NAME组为16．17+3．14与对照组比较,差异有显著性(P<0．05)。Western blot分析结果显示,L- NAME能明显抑制LS174T细胞裸小鼠移植瘤VEGF蛋白的表达,与对照组相比,都明显减弱(P<0．05)。结论:L—NAME 具有抑制肿瘤生长和对抗肿瘤新生血管生成的作用。更多还原

【Abstract】 Objective: To investigate the anticancer potential of an inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester(L-NAME) on the growth of colorectal cancer xenografts in nude mice vivo as well as on tumor-associated angiogenesis. Methods: Human colorectal cancer cell line SL174T was inoculated subcutaneously into nude mice, L-NAME was administered orally to mice three times every week for two weeks. Tumor change was recorded. Immunihistochemistry was used to detect expression of MVD, the protein of VEGF was detected by western blot. Results: In tumor implantation studies, every treatment group had inhibitory effects on tumor growth more than control group (P<0.01 ). The combination group showed inhibitory effects on tumor growth more than L-NAME group and 5-Fu group (P<0.01 ). The MVD of tumor in L-NAME treating group was significantly lower than that in control group(p<0.01), Expression of VEGF in L-NAME treating group was weaker than that in control group. Conclusion: Antiangiogenesis is one of the mechanisms by which L-NAME suppresses colorectal cancer proliferation.更多还原