丙氨瑞林对人子宫内膜癌裸鼠皮下移植瘤的生长及Fli-1表达的影响

发布时间：2018-04-03 08:48

  本文选题：子宫内膜癌　切入点：移植瘤　出处：《山西医科大学》2015年硕士论文

【摘要】：目的:通过在裸鼠皮下建成人子宫内膜癌的肿瘤模型,再对实验裸鼠随机分组后用不同剂量的丙氨瑞林干预,观察不同浓度的药物干预后人子宫内膜癌体外移植肿瘤的增长状况和移植肿瘤中的Fli-1蛋白表达情况。方法:把HEC-1B人子宫内膜癌细胞株(HEC-1B于体外培养)接种到4-6周龄雌性裸鼠右上肢近腋皮下,建立肿瘤模型。然后将裸鼠随机分为4组(每组8只),即丙氨瑞林药物高、中、低剂量组及生理盐水对照组。创建模型1周后对各组进行丙氨瑞林干预,每天肌肉注射药物1次,药量为每次0.2ml。低、中、高剂量组的药物浓度分别为20μg/kg、40μg/kg、80μg/kg,同时对照组给予肌注0.2ml生理盐水。严密观测肿瘤的增长情况,并察看裸鼠一般状况。4周后处死荷瘤小鼠,将肿瘤完整取出,计算各治疗组的抑瘤率,随后应用免疫组化察瘤细胞中Fli-1(弗里德白血病病毒插入位点1)的表达。结果:(1)荷瘤小鼠的一般情况裸鼠在建模之初,活动、反应好,体重变化不明显;在瘤体逐渐增大的过程中,裸鼠的反应力和活动力逐渐下降,体重日渐减轻。各治疗组裸鼠的反应力及体重都不同程度高于对照组。(2)药物干预后体肿瘤体积随药物剂量的增大,增长曲线的斜率变小,反映肿瘤的增长速度逐渐减慢,肿瘤的增长受到明显抑制。对照组、低、中、高剂量组肿瘤体积分别为:(1812.93±196.249mm3)、(1518.82±124.933mm3)、(1399.44±187.657mm3)、(1164.55±189.118mm3),各两组间比较,用LSD-t检验,差异具统计意义(F值为18.604,P0.001)。低、中、高剂量组的抑瘤率为(14.76±4.904%)、(27.5±5.456%)、(36.77±2.67%),用LSD-t检验,实验组各两组间比较,且与对照组相比,差异均有统计学意义(F值为31.477,P0.001)。说明丙氨瑞林对肿瘤细胞增长起抑制性作用,且有剂量依赖性。(3)HE染色结果治疗组中瘤细胞比较稀疏,能够看到裂解的、固缩的和凋亡细胞;对照组中瘤细胞密集,清晰可见癌巢,肿瘤细胞核大深染,大量核分裂相,胞核与胞浆比例极其失调。(4)免疫组化结果移植瘤用不同剂量药物干预后,随剂量增加Fli-1蛋白表达量逐渐减少。对照组及丙氨瑞林各治疗组肿瘤组织中Fli-1蛋白的灰度值分别为:对照组(118.1±4.241)、低剂量组(135.93±3.548)、中剂量组(147.51±6.755)、高低剂量组(168.84±5.202),与对照组比较,各治疗组中Fli-1蛋白表达水平灰度值都有不等级别的增高,且不同剂量的组间比较采用LSD-t检验差异有统计学意义(F=140.196,P0.001)。结论:(1)丙氨瑞林在裸鼠移植瘤发展中起抑制作用,伴随丙氨瑞林剂量增添的同时抑制作用越发明显。(2)丙氨瑞林对肿瘤的抑制作用机制可能与下调移植瘤组织中Fli-1的表达有关。
[Abstract]:Objective: to establish a tumor model of human endometrial carcinoma in nude mice subcutaneously.To observe the growth of human endometrial carcinoma transplanted tumor in vitro and the expression of Fli-1 protein in transplanted tumor after different concentrations of drugs.Methods: HEC-1B human endometrial carcinoma cell line HEC-1B was cultured in vitro.Then the nude mice were randomly divided into 4 groups (8 rats in each group), that is, alanine high, middle and low dose groups and normal saline control group.One week after the model was established, each group was treated with alarelin. The drug was injected intramuscularly once a day, with a dose of 0.2 ml per day.The drug concentrations in the low, middle and high dose groups were 20 渭 g / kg ~ 40 渭 g / kg ~ 80 渭 g 路kg ~ (-1) respectively, while the control group was given 0.2ml saline intramuscularly.The tumor-bearing mice were killed after observing the general condition of the nude mice for 4 weeks, the tumor was removed completely, and the tumor inhibition rate of each treatment group was calculated.The expression of Fli-1 (Fli-1) was detected by immunohistochemistry.Results (1) the general situation of tumor-bearing mice was that at the beginning of modeling, the nude mice reacted well, but their body weight did not change obviously, while the reaction power and activity force of nude mice gradually decreased and their body weight gradually decreased during the process of tumor increasing.The response power and body weight of nude mice in each treatment group were higher than those in control group (P < 0.05). The volume of body tumor decreased with the increase of drug dose, and the slope of the growth curve became smaller, which indicated that the growth rate of tumor was slowing down gradually.The growth of the tumor was significantly inhibited.瀵圭収缁，

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