奥希替尼联合地塞米松抑制非小细胞肺癌的有效性研究

发布时间：2018-03-10 22:03

  本文选题：奥希替尼　切入点：地塞米松　出处：《锦州医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的本实验通过体外细胞培养和荷瘤小鼠实验,观察抗癌新药奥希替尼联合地塞米松对肿瘤的抑制效果,分析其联合使用的优势,为临床联合用药及进一步研究复方制剂的制备提供相应的参考数据。方法以不同浓度的奥希替尼、地塞米松及两者联合用药的方式分别作用于非小细胞肺癌细胞株H1975。在24、48、72h后,应用四甲基偶氮唑蓝(MTT)比色法检测细胞增殖抑制情况;建立小鼠荷肺癌模型后,按照奥希替尼组、地塞米松组、联合用药组和对照组的分组模式连续测量小鼠肿瘤体积和小鼠体重,分别绘制肿瘤生长曲线和小鼠体重变化曲线,观察各药物组的作用效果。同时利用免疫组化S-ABC法测定各组对与炎症产生和肿瘤血管生成有关的HIF-1a及NF-κB的抑制情况,并将各组数据进行比较。结果通过MTT实验测得单独用药组和联合用药组对H1975细胞的抑制率,经SPSS数据分析,LSD数据比较发现,地塞米松不同药物浓度组在24h、48h以及72h的细胞抑制率均不存在显著性差异(P≥0.05);奥希替尼不同药物浓度组在24h、48h以及72h的细胞抑制率均存在显著性差异(P≤0.05);联合用药组对比于奥希替尼单独用药组在24h、48h以及72h的细胞抑制率不存在显著性差异(P≥0.05)。单独使用地塞米松和奥希替尼,其肿瘤体积和小鼠体重变化速度显著低于对照组,最优组为联合用药组,其肿瘤生长速度明显放缓,小鼠体重得到明显控制且与对照组和单独使用药物的试验组有显著性差异(P≤0.05)。通过免疫组化S-ABC法测定各组对HIF-1a及NF-κB的抑制强度,发现各组HIF-1a、NF-κB表达情况均有显著下降(P≤0.05)。联合用药组对HIF-1a、NF-κB表达抑制最强,且与对照组和单独使用药物的试验组有显著性差异(P≤0.05)。应用常规组织学染色法在显微镜下观察联合用药组处理后小鼠肿瘤块组织结构,对比单独使用奥希替尼组处理后小鼠肿瘤块组织结构,可以发现联合用药处理后的肿瘤块内部肿瘤血管明显减少,颜色发白。结论地塞米松对非小细胞肺癌细胞株H1975抑制效果不显著。奥希替尼对非小细胞肺癌细胞株H1975具有很强的抑制作用。相对于单独使用奥希替尼,联合地塞米松用药并没有增加对H1975的抑制效果。但地塞米松可显著降低HIF-1a、NF-κB的表达,近而抑制炎症和肿瘤血管的生成。相对于单独用药,联合用药可显著提高对HIF-1a、NF-κB表达的抑制效果,联合用药后肿瘤结构内血管明显减少,颜色发白。通过小鼠实验可以发现,联合用药可显著放缓肿瘤的生长速度,控制小鼠的体重,保持小鼠的精神状态。相对于单独用药,联合用药在诸多方面优势明显。
[Abstract]:Objective to observe the inhibitory effect of Ochitinib combined with dexamethasone on tumor and to analyze the advantages of combined use of omitinib and dexamethasone through cell culture in vitro and tumor-bearing mice. Methods different concentrations of omitinib, dexamethasone and the combination of two drugs were used to treat NSCLC cell line H1975.After 2448h, H1975cells were treated with different concentrations of omitinib and dexamethasone respectively. The inhibition of cell proliferation was detected by MTT colorimetric assay, and the model of lung cancer was established in mice, which was treated with oxitinib, dexamethasone, dexamethasone, dexamethasone, oxitinib, dexamethasone. The tumor volume and body weight of mice were measured continuously in the combination group and control group, and the tumor growth curve and the weight change curve of mice were drawn, respectively. At the same time, the inhibition of HIF-1a and NF- 魏 B related to inflammation and tumor angiogenesis was determined by immunohistochemical S-ABC method. Results the inhibition rate of H1975 cells in single drug group and combined drug group was measured by MTT experiment. The results showed that the inhibition rate of H1975 cell line was compared by SPSS data analysis. There was no significant difference in cell inhibition rate between 24 h and 72 h in different concentration groups of dexamethasone (P > 0.05), but there was significant difference in cell inhibition rate between 24 h and 72 h in different concentration groups of oxetinib (P 鈮，

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