摘要
目的：实验拟验证三氧化二砷与阿司匹林联用对人胃癌裸鼠皮下移植瘤血管生成的影响。方法：实验于2006-09／2007-07在徐州医学院病理实验室完成。①实验材料：雄性BALB／C-nu／nu裸小鼠36只，4—6周龄，体质量18-22g：人胃癌细胞株SGC-7901购自中科院上海生物研究所。②造模及分组：36只裸鼠建立人胃腺癌SGC-7901细胞株腋窝外侧皮下移植瘤模型。随机抽签法分为对照组、阿司匹林组、三氧化二砷组和联合治疗组，每组9只。③实验干预：接种后7d开始腹腔注射给药。对照组：无菌生理盐水0．2mL/d；阿司匹林组：给予阿司匹林0．3g/（kg·d）；三氧化二砷组：注射三氧化二砷2．5mg／（kg·d）：联合治疗组：三氧化二砷2．5mg／（kg·d）＋阿司匹林0．3g／（kg·d）。连续用药14d。④实验评估：以免疫组织化学SP法检测瘤组织内环氧合酶2和CD34的表达，并计数其微血管密度：以蛋白免疫印迹检测IKKa、IkB、核因子kB及血管内皮细胞生长因子的表达。结果：雄性BALB／C-nu／nu裸小鼠27只进入结果分析。接种7d后，31只裸鼠背部形成直径约1mm左右的肿瘤。用药后，三氧化二砷组、联合治疗组各有1只裸鼠死亡：阿司匹林组有1只死亡，1只丢失。①联合用药组与阿司匹林组、三氧化二砷组及对照组相比，IKKa、核因子kB和血管内皮细胞生长因子表达均减少（P〈0．05），IkB表达增高（P〈0．05）。②联合治疗组移植瘤微血管密度与其他3组相比，差异具有显著性意义（P〈0．05）。⑨联合治疗组环氧合酶2表达率最低，与其他3组相比，差异有显著性意义（P〈0．05）。结论：三氧化二砷和阿司匹林联用的协同作用降低了核因子kB、环氧合酶2、血管内皮细胞生长因子的表达，从而抑制肿瘤血管生成。
AIM： The study aimed to verify the effects of arsenic trioxide in combination with aspirin on angiogenesis of human gastric cancer xenografts in nude mice. METHODS： Experiments were performed at the Laboratory of Pathology, Xuzhou Medical College from September 2006 to July 2007. A total of 36 male BALB/C-nu/nu nude mice aged 4-6 weeks, weighting 18-22 g were selected. Human gastric cancer cell strain SGC-7901 were purchased from Shanghai Institute of Biology of Chinese Academy of Sciences. Thirty-six nude mouse models of cell strain SGC-7901 lateral armpit subcutaneously transplantation tumor were established and randomized into a control group, a aspirin group, a arsenic trioxide group and a combination group with nine in each group. Seven days after inoculation, nude mice were intraperitoneally administrated with drugs. Nude mice in the control group were treated with sterile saline （0.2 mL/d）; Mice in the aspirin group were administrated with aspirin 0.3 g/（kg · d）; Mice in the arsenic trioxide group received 2.5 mg/（kg · d）; Mice in the combination group were administrated with 2.5 mg/（kg · d）plus aspirin 0.3 g/（kg · d）, successively for 14 days. Immunohistochemical method （SP kit） was used to detect the expression of cycloxygenase-2 （COX-2） and CD34, and count microvessel density （MVD）. Western-blotting was used to detect the expression of IKK a, I k B, nuclear factor （NF）- k B and vascular endothelial growth factor （VEGF）. RESULTS： A total of 27 male BALB/C-nu/nu nude mice were included in the final results. Seven days after inoculation, 1 mm tumor was formed on the back of 31 nude mice. One mouse respectively died in the arsenic trioxide group and the combination group One mouse died and one loss in the aspirin group. Compared to the aspirin group, arsenic trioxide group and control group, expressions of IKK a, NF- k B and VEGF decreased in the combination group （P 〈 0.05）, but I k B levels increased （P 〈 0.05）. Compared to other groups, there were significant differences in MVD in the combination group （P 〈 0.05）. COX-2 expression reduced in the combination group compared to other groups （P 〈 0.05）. CONCLUSION： Arsenic trioxide in combination with aspirin can inhibit tumor neovascularity by further inhibiting NF- k b, COX-2 and VEGF expressions.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2008年第33期6434-6438,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
江苏省教育厅高校自然科学基金(06KJB310118)~~
