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苏拉明联合人参皂苷Rg3抑制肺腺癌小鼠移植瘤生长的作用

贺兼斌   

  1. 湖南省怀化市第一人民医院（南华大学附属怀化医院）呼吸内科
  • 收稿日期:2012-11-26 修回日期:2013-04-26 出版日期:2013-09-15 发布日期:2013-09-15
  • 通讯作者: 贺兼斌

nhibitory Effects of Suramin in Combination with PG-Rg3on the Growth of Lung Adencarcinoma in Mice

HE Jian bin   

  1. Department of Respiration, First People’s Hospital of Huaihua
  • Received:2012-11-26 Revised:2013-04-26 Published:2013-09-15 Online:2013-09-15
  • Contact: HE Jian bin

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摘要：

【摘要】目的  观察苏拉明联合人参皂苷Rg3（PG-Rg3）对肺腺癌小鼠异体移植瘤生长的抑制作用，初步探讨其相关机制。方法  构建肺腺癌小鼠移植瘤模型，将40只接种Lewis肺癌细胞的C57BL/6J小鼠随机分成5组：对照组、顺铂（DDP）组、苏拉明组、PG-Rg3组、苏拉明+ PG-Rg3组（联合组）。给予相应药物干预，于接种后24d处死，剥离皮下肿瘤，免疫组化和图像分析系统检测皮下移植瘤中肝细胞瘤扩增序列（Eph）受体家族EphB4蛋白、B细胞淋巴瘤/白血病-2（Bcl-2）蛋白表达及微血管密度（MVD），并检测肿瘤细胞凋亡情况。结果  各用药组皮下肿瘤体积、质量低于对照组（P<0.05），顺铂组、苏拉明组、PG-Rg3组、联合组的抑瘤率分别为39.20%、49.11%、54.86%、62.49%。与对照组及DDP组比较，苏拉明组、PG-Rg3组和联合组EphB4、Bcl-2灰度值及MVD明显降低，而凋亡指数明显升高（均P<0.05）。与联合组比较，苏拉明组、PG-Rg3组EphB4、Bcl-2灰度值及MVD增加，而凋亡指数减少（均P<0.05）。结论  苏拉明和PG-Rg3对肺腺癌移植瘤的生长具有协同抑制作用，其机制与其抑制肿瘤内EphB4表达，抑制微血管形成，促进肿瘤细胞凋亡有关

关键词: 肺肿瘤, 腺癌, 原癌基因蛋白质c-bcl-2, 受体, EphB4, 细胞凋亡, 免疫组织化学, 小鼠

Abstract:

[Abstract]  Objective   To observe the effect of suramin combinated with PG-Rg3on xenograft growth of lung adeno- carcinoma in mice, and the related mechanism thereof.  Methods   Forty C57BL/6J mice bearing Lewis cells were random?ized into five groups: control group, cisplatin (DDP) group, suramin group, PG-Rg3group and combination group. Appropriate interventions were given in five groups of mice. Mice were sacrificed at day24after tumor inoculation. The subcutaneous tumors were stripped for histological examination. The tumor inhibitory rate was measured. The expressions of erythropoietinproducing hepatoma amplified sequences (Eph) B4protein, Bcl-2and tumors microvessel density (MVD) were determined by immunohistochemistry method with image analyze system. The apoptosis of tumor cells was measured by biotinyated dUTP nick and labeling (TUNEL) method.  Results   There were significantly lower values in subcutaneous tumor volume and weight in drug-treated groups than those in control group (P<0.05). The inhibitory rates were39.20%,49.11%,54.86% and62.49% in cisplatin group, suramin group, PG-Rg3group and combined group (P<0.05). The values of EphB4, MVD and Bcl-2grey values were significantly decreased, the apoptotic index was significantly increased, in suramin group, PGRg3group and combined group than those of control group and DDP group (P<0.05). The values of EphB4, MVD and Bcl-2 grey values were significantly increased, the apoptotic index was significantly decreased, in suramin group and PG- Rg3 group than those of combined group (P<0.05).   Conclusion   Suramin combinated with PG-Rg3can produce a synergetic inhibitory activity against tumor growth of lung adenocarcinoma, which may be associated with the effect of suppressing the expression of EphB4and angiogenesis, and the promotion of tumor cell apoptosis

Key words: lung neoplasms, adenocarcinoma, proto-oncogene proteins c-bcl-2, receptor, EphB4, apoptosis, immunohistochemistry, 小鼠