^(125)I粒子植入对人纤维肉瘤裸鼠皮下移植瘤微血管生成的影响

Effect of ^(125)I Seeds Brachytherapy on the Angiogenesis in Human Fibrosarcoma Xenografts in Nude Mice

目的观察不同活度的125I粒子植入对人纤维肉瘤裸鼠移植瘤微血管生成的影响。方法建立人纤维肉瘤细胞HT-1080裸鼠皮下移植瘤模型24只,随机分4组,实验组A、B、C组分别植入单颗活度为14.8、22.2、29.6MBq的125I粒子,对照组D组植入单颗空源。15d后比较各实验组及对照组之间移植瘤大小,计算抑瘤率,观察移植瘤微血管结构的变化及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达,比较各组微血管密度(microvascular density,MVD)。结果粒子植入后15d,A、B、C、D组的肿瘤体积分别为:(879.32±54.90)mm3、(186.91±32.70)mm3、(122.01±34.72)mm3和(1302.71±62.39)mm3,各组差异均有统计学意义(F=844.21,P=0.000)。125I粒子对A、B、C组肿瘤体积抑制率分别为32.50%、85.65%和90.63%。与D组比较,实验组可见移植瘤细胞坏死,微血管不同程度减少,内皮细胞杀伤明显。4组VEGF表达阳性率分别为54.2%(13/24)、29.2%(7/24)、20.8%(5/24)、66.7%(16/24),A、D组间VEGF表达差异无统计学意义(χ2=0.784,P=0.376),B、C组的VEGF表达均显著低于D组,差异有统计学意义(χ2=6.762,P=0.009;χ2=10.243,P=0.001),A、C组与B组VEGF表达比较,差异均无统计学意义(χ2=3.086,P=0.079;χ2=0.444,P=0.505),A、C组比较,VEGF表达差异具有统计学意义(χ2=5.689,P=0.017)。4组MVD表达分别为(27.49±3.10)个、(10.27±3.57)个、(9.14±2.49)个、(30.15±4.26)个,差异具有统计学意义(F=253.22,P=0.000),A、D组间MVD表达差异无统计学意义(q=3.814,P>0.05),但B、C组的MVD表达均显著低于D组,差异有统计学意义(q=28.502,P<0.05;q=30.123,P<0.05)。B、C组与A组表达MVD比较,差异有统计学意义(q=24.689,P<0.05;q=26.309,P<0.05),B、C组间比较差异无统计学意义(q=1.628,P>0.05)。结论 125I粒子组织间植入对人纤维肉瘤微血管生成有显著抑制作用,粒子初始活度影响治疗效果。

Objective To investigate the effect of 125I radioactive seed implantation on the angiogenesis in nude mice with trans-planted human fibrosarcoma.Methods Animal models simulating human fibrosarcoma was established by subcutaneous implantation of HT-1080 cell lines into 24 nude mice.The mice were randomly divided into 4 groups：group A,B,C,and group D（control）,which were respectively treated with different activities of 125I seed：14.8,22.2,29.6 and 0 MBq.The tumor growth inhibitory rate,change of microvascular structure,vascular endothelial growth factor（VEGF）and microvascular density（MVD）were detected respectively on the 15th day after the 125I seed implantation.Results On the 15th day after the 125I seed implantation,the average tumor volume of group A,B,C and D were（879.32±54.90）,（186.91±32.70）,（122.01±34.72）and（1302.71±62.39）mm3.There were significant differences between the groups（F=844.21,P=0.000）.The tumor growth inhibitory rate in groups A,B,and C were 32.50%,85.65% and 90.63%,respectively.Compared with the control group,experimental groups showed tumor cell necrosis,various degrees of reduction in microvascular endothelial cells.The positive rate of VEGF expression in the four groups were 54.2%（13/24）,29.2%（7/24）,20.8%（5/24）,and 66.7%（16/24）,respectively;no significant difference was noticed between groups A and D（χ2=0.784,P=0.376）;whereas,the expression levels in groups B and C were significantly lower than that in group D（B vs D,χ2 =6.762,P=0.009;and C vs D,χ2=10.243,P=0.001）.In addition,no significant difference in VEGF expression was detected between group B and groups A or C（χ2=3.086,P=0.079 and χ2=0.444,P=0.505）,while between groups A and C,significant difference was observed（χ2=5.689,P=0.017）.In the four groups,the MVD was（27.49±3.10）,（10.27±3.57）,（9.14±2.49）,and（30.15±4.26）,respectively;no significant difference was found between groups A and D（q=3.814,P0.05）;whereas significant difference was found between groups B and D（q=28.502,P0.05）,C and D（q=30.123,P0.05）,B and A（q=24.689,P0.05）,and C and A（q=26.309,P0.05）.ConclusionsInterstitial implantation with 125I seed has significant effect on angiogenesis of the human fibrosarcoma xenografts in nude mice,and the initial activities of the 125I seed can affect the effectiveness of the treatment.