多西他赛联合希罗达对大鼠乳腺癌癌前病变组织 MVD、TGF-α与VEGF表达的影响

摘要

目的：探讨多西他赛联合希罗达对乳腺癌癌前病变组织微血管密度、转化生长因子-1及血管内皮生长因子表达的影响。方法：将350只SD大鼠随机分为7组。采用二甲基苯蒽诱导大鼠乳腺癌癌前病变，进行4周干预治疗，从第8周开始开始将大鼠处死并进行病理学分析。采用免疫组化检测MVD和TGF-α的表达情况、原位杂交法测定VEGF mRNA的表达。结果：造模组的死亡率和癌前病变发生率均明显较高；多西他赛联合希罗达的大剂量和中剂量组的癌前病变的发生率明显较低；各组不同病变类型组织中的MVD、TGF-α及VEGF mRNA的阳性表达率均呈递增趋势；在非典型增生组中，大剂量组、中剂量组及多西他赛组的MVD与TGF-α的阳性表达率均明显较低，各干预组的VEGF mRNA的阳性率均明显较低；对于VEGF mRNA的阳性率的非典型增生，大剂量组中的VEGF mRNA的阳性率明显低于小剂量组（ P＜0.05）。结论：多西他赛联合希罗达能够抑制乳腺癌的癌前病变的血管生成及相关调控因子TGF-α的表达，降低DMBA诱导的大鼠的乳腺癌癌前病变组织中的VEGF mRNA表达量。%Objective:To explore the reversal effect of Docetaxel and Capecitabine on rat breast precancerous from angiogenesis and expression of related regulatory factors VEGF mRNA in rats.Methods: 350 SD rats were divided into 7 groups.Model of rats mammary was induced by DMBA and was treated by Docetaxel and Capecitabine for 4 weeks.All of them were killed from 8th week.The microvascular were detected in the specimens, examination of histopathology was performed and the expression of VEGF mRNA was measured by in situ hybridization.Results:The rat mortality and the incidence of precancerous lesions increased obviously, and the incidence of precancerous lesion of the high-dose group and the middle dose reduced.The positive rate of the expression of MVD,TGF-αand VEGF mRNA tend to increase in all the groups.The positive-cell rate of VEGF mRNA of Docetaxel,Capecitabine, Docetaxel and Capecitabine in ADH was lower than in the model group,and the positive-cell rate of VEGF mRNA of Docetaxel and Capecitabine was lower than Capecitabine and Docetaxel separately.Conclusion: Combination of Docetaxel and Capecitabinecan decrease the expression of VEGF mRNA in precancerouslesion of rats mammary.