苏拉明联合阿霉素对肺腺癌小鼠移植瘤组织中bFGF和NF-К Bp65表达的调控及意义

Study of Suramin in combination with Adriamycin and its efficacy on the bFGF and NF-КBp65 in the transplantation of Lung-adenocarcinoma of mice

目的探讨苏拉明联合阿霉素对肺腺癌小鼠移植瘤组织中碱性成纤维细胞生长因子(bFGF)和核因子-КBp65(NF-КBp65)表达的调控及意义。方法复制肺腺癌LA795细胞的T739小鼠异体移植瘤模型。40只实验小鼠皮下移植处均成瘤,接种后4d随机分为4组,每组10只。对照组:生理盐水0.2mL/只,于接种后第4天开始腹腔注射,1次/d,共16次;阿霉素组:阿霉素[2mg/(kg·d)]溶于0.2mL生理盐水中,于接种后第4、11和18天各腹腔注射一次;苏拉明组:苏拉明[10mg/(kg·d)]溶于0.2mL生理盐水中,余同对照组;联合组(阿霉素+苏拉明):按阿霉素组和苏拉明组用药。24d后处死,取肺组织观察肺转移例数,计数肺转移率及肺转移结节数;收集肿瘤标本固定,用免疫组化和图像分析系统定量检测肿瘤组织bFGF和NF-КBp65的表达,用TUNEL原位凋亡法检测移植瘤组织中肿瘤细胞,计算凋亡指数。结果联合组与苏拉明组肺转移率低于对照组,以联合组最低,联合组差异有显著性,苏拉明组差异无显著性。各治疗组肺转移结节数均低于对照组,以联合组最低,差异均有显著性;bFGF灰度值、NF-КBp65灰度值和凋亡指数均高于对照组,以联合组最高,差异均有显著性。各组间bFGF灰度值与肺转移结节数呈反向变化,直线相关分析显示均呈负相关,NF-КBp65灰度值与凋亡指数呈同向变化,作直线相关分析显示均呈正相关。结论阿霉素可能协同苏拉明通过抑制bFGF和NF-КBp65的表达,从而抑制肿瘤细胞转移,促进肿瘤细胞凋亡。

[Objective] To study the regulation of Suramin in combination with Adriamycin and its efficacy on the bFGF and NF-KBp65 in the transplantation of Lung-adenocareinoma of mice. [Methods] LA795 cells were subcutaneously inoculated into the mammary fatty pad of T739 mice to clone lung ad model, after the treatment, 40 experimental mice were randomized into four groups （ten in each group）. Control group： every mouse was injected into penealiy with 0.2ml 0.9%sedium chloride aqua everyday, 16 times in all days. Adriamycin groups： every mouse was injected into abdominal cavity with Adriamycin dissolvied in sodium chloride aqua for 2 mg/（kg.d） on the 4th ,11th ,18th days. Suramin groups： every mouse was injected abdominal cavity with Suramin dissolved in sodium chloride aqua for 10 mg/（kg.d） a time/day, 16 times in all days. Alliace groups： the dose is consisted with those of in Adriamycin groups and Suramin groups, after transplantation and all mice were sacrificed after 24 days, Lung tissues were taked to Observe the lugn shifted example number, calcutate the lugn transfer rate and the lung shifts the tubercle number, tumor specimens collected fixed, using immunohistochemistry and image analysis system for quantitative detection of tumor tissue bFGF and NF-KBp65 expression, TUNEL method to detect tissue tumor cell apoptosis index [Results] Alliace group and suramin group lung metastasis rate lower than the control group, with the lowest combined group, the difference was significant. The treatment group metastatic nodules were lower than the control group, with the lowest Alliace group, the difference was significant in Alliace groups, but the difference was not significant in Suramin groups, bFGF gray value, NF-KBp65 gray values and apoptosis index were significantly higher, with the highest Alliace groups, the difference was significant. The group bFGF gray values with metastatic nodules inversely to changes in linear correlation analysis showed a significant negative correlation, NF-KBp65 gray values and apoptosis index was the same changes to make linear correlation analysis showed a positive correlation. [Conclusions] Adriamycin possible synergy Suramin through suppresses bFGF and NF- K Bp65 expression, thus the suppression tumor cell shift, the promotion it＇ apoptosis index.