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贝伐单抗结合紫杉醇对肺癌小鼠的治疗效果及对癌组织S100A4和MMP-9的影响
引用本文:毛卫波,朱忆凌,严礼平,周佳慧,黄渊,陈国荣.贝伐单抗结合紫杉醇对肺癌小鼠的治疗效果及对癌组织S100A4和MMP-9的影响[J].温州医科大学学报,2020,50(7):573-577.
作者姓名:毛卫波  朱忆凌  严礼平  周佳慧  黄渊  陈国荣
作者单位:1.温州医科大学附属第五医院丽水市中心医院病理科,浙江丽水323000;2.温州医科大学附属第一医院病理科,浙江温州325015
摘    要:目的:探讨贝伐单抗结合紫杉醇对C57BL/6肺癌小鼠的治疗效果及对癌组织S100A4与MMP-9的影响。方法:应用鼠源性Leweis肺癌瘤株制备瘤液,对SPF级健康C57BL/6小鼠进行分组,将实验小鼠分为正常组(未接种瘤液)、模型组(接种瘤液)、贝伐单抗组(接种瘤液)、紫杉醇组(接种瘤液)、联合组(接种瘤液),每组8只。正常组和模型组腹腔注射0.9%氯化钠溶液;贝伐单抗组腹腔注射15 mg/kg贝伐单抗;紫杉醇组腹腔注射10 mg/kg紫杉醇;联合组分别腹腔注射15 mg/kg贝伐单抗和10 mg/kg紫杉醇。所有小鼠2周后处死,摘眼球取血和取瘤称重。比较各组小鼠的抑瘤率,酶联免疫吸附法检测IL-2、IL-6、TNF-α、VEGF、S100A4与MMP-9含量,流式细胞技术检测T淋巴细胞亚群,Western blot法测定VEGF水平。结果:治疗后,贝伐单抗组、紫杉醇组、联合组瘤重,IL-2、IL-6及TNF-α含量、VEGF水平、S100A4与MMP-9含量显著低于模型组,联合组抑瘤率明显高于贝伐单抗组和紫杉醇组,差异均有统计学意义(P<0.05);联合组IL-2、IL-6及TNF-α含量、VEGF水平、S100A4与MMP-9含量显著低于贝伐单抗组,差异均有统计学意义(P<0.05)。贝伐单抗组、紫杉醇组以及联合组的CD3+、CD4+、CD8+、CD4/CD8的含量与模型组比较,差异有统计学意义(P<0.05)。结论:贝伐单抗结合紫杉醇能抑制C57BL/6肺癌小鼠肿瘤的生长,能改善其免疫功能,降低VEGF、S100A4与MMP-9的含量。

关 键 词:贝伐单抗  紫杉醇  Lewis肺癌  血管内皮生长因子  S100钙结合蛋白A4  基质金属蛋白酶  

Therapeutic effect of bevacizumab combined with paclitaxel on lung cancer in mice and its effect on S100A4 and MMP-9 in cancer tissue
Mao Weibo,Zhu Yiling,Yan Liping,Zhou Jiahui,Huang Yuan,Chen Guorong.Therapeutic effect of bevacizumab combined with paclitaxel on lung cancer in mice and its effect on S100A4 and MMP-9 in cancer tissue[J].JOURNAL OF WENZHOU MEDICAL UNIVERSITY,2020,50(7):573-577.
Authors:Mao Weibo  Zhu Yiling  Yan Liping  Zhou Jiahui  Huang Yuan  Chen Guorong
Institution:1.Department of Pathology, Lishui Central Hospital, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; 2.Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
Abstract:Objective: To investigate the therapeutic effect of bevacizumab combined with paclitaxel on C57BL/6 lung cancer mice and the effect on cancer tissues S100A4 and MMP-9. Methods: Using rat-derived Leweis lung cancer tumor strains to prepare tumor fluid, SBF level healthy C57BL/6 mice were divided into normal group (uninoculated tumor fluid), model group (inoculated tumor fluid), bevacizumab group (inoculated tumor fluid), paclitaxel group (inoculated tumor fluid), and bevacizumab combined paclitaxel group (inoculated tumor fluid), with 8 cases in each group. The normal group and the model group were intraperitoneally injected with normal saline twice a week, while bevacizumab group with 15 mg/kg bevacizumab twice a week, the paclitaxel group with 10 mg/kg paclitaxel twice a week; The combination group was intraperitoneally injected with 15 mg/kg bevacizumab and 10 mg/kg paclitaxel twice a week. All mice were killed 2 weeks later, and the eyeballs were taken for blood and weighed. The tumor inhibition rate, IL-2, IL-6, TNF-α, VEGF, S100A4 and MMP-9 contents were detected by enzyme linked immunosorbent assay, T lymphocyte subsets by flow cytometry and VEGF levels by Western blot method. Results: After treatment, the tumor weight, the content of IL-2, IL-6 and TNF-α, VEGF, S100A4 and MMP-9 in bevacizumab group, paclitaxel group and combination group was significantly lower than those in model group, the tumor inhibition rate in combination group was higher than those in bevacizumab group and paclitaxel group, while the content of IL-2, IL-6 and TNF-α, VEGF, S100A4 and MMP-9 in bevacizumab group was significantly lower than those in bevacizumab group (P<0.05). The content of CD3+, CD4+, CD8+ and CD4/CD8 in bevacizumab group, paclitaxel group and combination group was significantly different from those in model group (P<0.05). Conclusion: Bevacizumab combined with paclitaxel can inhibit the growth of C57BL/6 lung cancer in mice, improve their immune function, and reduce the level of vascular endothelial growth factor, S100A4 and MMP-9.
Keywords:bevacizumab  paclitaxel  Lewis lung carcinoma  vascular endothelial growth factor  S100 calcium binding protein A4  matrix metalloproteinase-9  
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