三阴性乳腺癌模型裸鼠血管正常化后对紫杉醇的反应

发布时间：2018-05-13 17:27

本文选题：三阴性乳腺癌 + 血管正常化　；参考：《中国病理生理杂志》2017年10期

【摘要】：目的:通过观察人三阴性乳腺癌(triple-negative breast cancer,TNBC)模型裸鼠血管正常化后对紫杉醇的反应,探讨重组人内皮抑素与紫杉醇在血管正常化时间窗内联用是否优于紫杉醇单用并分析磁共振成像(magnetic resonance imaging,MRI)在早期评估化疗的作用。方法:将人TNBC细胞株MDA-MB-231种植于36只BALB/c-nu雌性裸小鼠的右下腹部皮下,随机分成4组(模型组、重组人内皮抑素治疗组、紫杉醇治疗组及人内皮抑素联用紫杉醇治疗组),每组有7只完成实验。重组人内皮抑素于实验开始时给药,连续使用17 d,紫杉醇于实验第6天和第12天分别给药,所有用药均为腹腔注射,用量均为10 mg·kg~(-1)·d~(-1)。治疗前1 d及注射实验试剂后5、11、17 d进行MRI扫描,所有荷瘤鼠均在最后一次MRI扫描后颈椎脱位处死,切下瘤体,进行病理学及免疫组化检测,测定肿瘤微血管密度(microvessel density,MVD)及Ki67表达。结果:第17天,联用组移植瘤体积小于模型组及重组人内皮抑素治疗组(P0.05),但与紫杉醇治疗组比较无显著差异。第11天,紫杉醇治疗组的慢弥散系数大于模型组,联用组慢弥散系数大于重组人内皮抑素治疗组(P0.05)。解剖各组荷瘤鼠未见远处转移病灶。HE染色显示4组肿瘤外周均有明显坏死,且药物治疗组坏死程度均高于模型组。药物治疗组的MVD均小于模型组,且药物联用组均小于药物单用组(P0.05)。药物联用组Ki67表达较重组人内皮抑素组明显降低,但与紫杉醇治疗组相比无显著差异。结论:在血管正常化时间窗内,重组人内皮抑素联合紫杉醇化疗对TNBC移植瘤虽有明显的抑瘤作用,但疗效未优于紫杉醇;慢弥散系数可以早期预测治疗效果。
[Abstract]:Objective: to observe the response to paclitaxel in nude mice with triple-negative breast cancer TNBC- (tri-negative breast cancer) model. To investigate whether the combination of recombinant human endostatin and paclitaxel in vascular normalization time window is superior to paclitaxel alone and to analyze the role of magnetic resonance imaging (MRI) in the early evaluation of chemotherapy. Methods: human TNBC cell line MDA-MB-231 was implanted in the right lower abdomen of 36 female BALB/c-nu nude mice and was randomly divided into 4 groups (model group, recombinant human endostatin treatment group). Paclitaxel treatment group and human endostatin combined with paclitaxel treatment group, 7 rats in each group completed the experiment. Recombinant human endostatin was administered at the beginning of the experiment for 17 days and paclitaxel was administered on the 6th and 12th day respectively. All the drugs were intraperitoneally injected with the dosage of 10 mg 路kg ~ (-1) 路d ~ (-1) 路L ~ (-1) 路d ~ (-1) 路min ~ (-1) 路d ~ (-1) 路L ~ (-1) 路L ~ (-1). MRI scanning was performed 1 day before treatment and 51117 days after injection of experimental reagent. All the tumor-bearing mice were killed after the last MRI scan, the tumor was removed, the tumor was examined by pathology and immunohistochemistry, the microvessel density (MVD) and the expression of Ki67 were measured. Results: on the 17th day, the volume of transplanted tumor in combination group was smaller than that in model group and recombinant human endostatin treatment group (P 0.05), but there was no significant difference compared with paclitaxel group. On the 11th day, the slow diffusion coefficient of paclitaxel group was higher than that of model group, and that of combination group was higher than that of recombinant human endostatin treatment group (P 0.05). No distant metastases were found in the tumor bearing mice in each group. He staining showed that the tumor periphery of the four groups were obviously necrotic, and the necrosis degree of the drug treatment group was higher than that of the model group. The MVD of the drug treatment group was lower than that of the model group, and that of the combined drug group was lower than that of the drug monotherapy group (P 0.05). The expression of Ki67 in the combined drug group was significantly lower than that in the recombinant human endostatin group, but there was no significant difference compared with the paclitaxel group. Conclusion: in the time window of vascular normalization, recombinant human endostatin combined with paclitaxel chemotherapy has obvious inhibitory effect on TNBC transplanted tumor, but the curative effect is not better than paclitaxel, and slow dispersion coefficient can predict the therapeutic effect early.
【作者单位】：暨南大学附属第一医院乳腺外科;暨南大学附属第一医院影像学科;暨南大学附属第一医院胃肠外科;暨南大学附属第一医院病理科;
【基金】：国家自然科学基金资助项目(No.81472849)
【分类号】：R-332;R737.9

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