贝伐单抗联合紫杉醇对黏液表皮样癌裸鼠移植瘤影响的实验研究

发布时间：2018-03-25 12:04

  本文选题：黏液表皮样癌　切入点：紫杉醇　出处：《昆明医科大学》2014年硕士论文

【摘要】：目的：研究贝伐单抗联合紫杉醇对裸鼠黏液表皮样癌移植瘤的治疗作用,探讨贝伐单抗和紫杉醇的抑瘤作用,研究靶向治疗在黏液表皮样癌中的应用,为临床治疗黏液表皮样癌提供理论依据。 材料和方法：1.构建裸鼠黏液表皮样癌移植瘤模型。通过BALB/c裸鼠右腋下注射1×106个黏液表皮样癌细胞,观察成瘤情况。成瘤两周后随机分为四组,每组7只裸鼠,对各组裸鼠进行药物干预,分别为空白组(生理盐水0.2m1/只/日)、紫杉醇组(紫杉醇10mg/kg/3d)、贝伐单抗组(贝伐单抗5mg/kg/d)、联合组(紫杉醇10mgmg/kg/3d+贝伐单抗5mg/kg/d)。记录裸鼠体重变化及瘤体尺寸,3天/次。两周后开始注射药物,四周时处死,剥离瘤体,称重计算抑瘤率,绘制肿瘤生长曲线。2.在荷瘤鼠身上测量移植瘤的长径(a)、短径(b)、高(c)。在处死裸鼠后通过排水法测出移植瘤近似真实体积,比较目前常用的四种移植瘤体积计算方法(π abb/6、abb/2、aab/2、πabc/6)与移植瘤真实体积之间的差异。3.制作石蜡切片,TUNNEL标记检测各组肿瘤细胞凋亡率。4.免疫组化法检测各组中肿瘤微血管密度的情况及各组的肿瘤微血管形成拟态的表达。采用SPSS13.0统计软件进行统计分析。 结果： 1.裸鼠体重变化情况：实验结束时各组裸鼠体重分别为空白组：24.32±2.22g；紫杉醇组20.83±1.70g；贝伐单抗组22.36±3.02g；和联合组23.00±3.03g。其中除联合组与贝伐单抗组差异不显著外(P0.05),其余各组间比较差异均有显著性(P0.05)。 2.瘤体重量及抑瘤率结果：四个组的瘤体重量分别是：空白组2.13±0.71g；紫杉醇组0.90±0.54g；贝伐单抗组1.51±0.69g；联合组0.85±0.35g。空白组与三个实验组之间瘤重存在显著性差异(P0.05),其余各组间比较瘤重差异无显著性(P0.05)。紫杉醇组、贝伐单抗组和联合组的肿瘤抑瘤率分别是57.75%；29.58%和60.09%。 3通过比较各组瘤体体积发现,在体经π abc/6公式计算得到的移植瘤体积结果与真实值之间差异无显著性(P0.05)。 4.移植瘤体积变化情况及体积大小比较：各实验组中,仅空白组体积在药物干预后其变化较大,其余各组在药物干预后各组体积变化较小。各组处死时移植瘤体积为空白组2000±577.4mm3；紫杉醇组1212.5±352.1mm3；贝伐单抗组1380±540.3mm3；联合组1120±840.3mm3。空白组与各实验组间比较差异有显著性(P0.05),其余各组间比较差异无显著性(P0.05)。 5.移植瘤细胞凋亡结果：四个组的IHS分别为：空白组3.60±1.04；紫杉醇组6.00±0.71；贝伐单抗组3.40±1.94；联合组6.40±2.51。空白组与紫杉醇组和联合组比较时(P≤0.05),差异有显著性,而与贝伐单抗组比较时(P0.05),差异无显著性。紫杉醇组与联合组比较时候(P0.05),差异无显著性,而与贝伐单抗组比较时(P0.05),差异有显著性。 .6各组移植瘤中MVD及VM表达情况：四个组的MVD分别为：空白组空白组27.8±4.0；紫杉醇组24.4±5.6；贝伐单抗组15.8±3.5；联合组14.2±2.2,空白组与紫杉醇组间差异无统计学意义(P0.05),贝伐单抗组与联合组间差异无统计学意义(P0.05)。其余各组间比较差异变化均具有显著性(P0.05),同时黏液表皮样癌内存在血管拟态现象。 结论1.紫杉醇或贝伐单抗均能抑制黏液表皮样癌裸鼠皮下移植瘤的生长,单独使用时紫杉醇效果较贝伐单抗明显,二者联合使用时效果最佳。2.贝伐单抗主要通过降低肿瘤内微血管密度达到抗肿瘤效果,而紫杉醇则主要是通过诱导肿瘤内细胞凋亡发挥抗癌作用,二者联用时可将药物作用发挥到最大。3..黏液表皮样癌内有三种血供模式即：内皮依赖性血管和血管生成拟态,以及马赛克血管。4.裸鼠皮下移植瘤体积计算最佳方法为πabc/6。
[Abstract]:Objective: To study the therapeutic effect of bevacizumab combined with paclitaxel on the xenograft of mucoepidermoid carcinoma in nude mice, and to explore the anti-tumor effect of bevacizumab and paclitaxel, and to study the application of targeted therapy in mucoepidermoid carcinoma, so as to provide a theoretical basis for the clinical treatment of mucoepidermoid carcinoma.
Materials and methods: 1. construction of xenograft model of mucoepidermoid carcinoma in nude mice. BALB/c mice through right axillary injection of 1 x 106 mucoepidermoid carcinoma cells, the tumor growth was observed. Tumor formation after two weeks were randomly divided into four groups, each group of 7 mice, drug intervention groups were divided into blank group (nude mice. Saline 0.2m1/ per day), paclitaxel group (paclitaxel 10mg/kg/3d), bevacizumab group (bevacizumab combined group (5mg/kg/d), paclitaxel 10mgmg/kg/3d+ 5mg/kg/d bevacizumab). Noted changes in body weight and tumor size, 3 days / times. Two weeks after the start of injection drugs around at the tumor body. Weighed to calculate the inhibition rate, tumor growth curve of.2. in tumor bearing mice measured the tumor diameter (a), short diameter (b), high (c). The mice were killed after the drainage measure tumor approximation of the real volume calculation method for the four kinds of tumor volume ( PI abb/6, abb/2, aab/2, n abc/6) and the difference between the true volume of transplanted tumor.3. in paraffin, TUNNEL markers for the detection of apoptosis of tumor cells was detected by.4. immunohistochemical tumor and tumor microvessel density in each group of angiogenesis mimicry expression. Statistical analysis was performed using SPSS13.0 software.
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