放疗联合^(125)I粒子植入对荷肺癌裸鼠肿瘤生长抑制作用的实验研究

The Inhibitory Effects of Radiotherapy Combined with ^(125)I Seed Brachytherapy on the Growth of Transplanted Human Lung Cancer Cell Line A549 in Nude Mice

目的研究放疗联合125I粒子植入对荷肺癌裸鼠肿瘤生长的抑制作用。方法应用裸鼠建立肺腺癌A549移植瘤模型,待平均瘤体积达到(300±50)mm3时,将40只裸鼠随机分成4组(每组10只),对照组:不做任何处理;单纯放疗组:第1天给予单次外照射,6MV-X线,10Gy;125I粒子植入组:于肿瘤中心植入1枚活度27.75MBq的125I粒子;放疗加125I粒子植入组(联合治疗组):第1天在肿瘤中心植入1枚活度27.75MBq的125I粒子的同时予单次外照射,6MV-X线,10Gy。治疗后共观察15d,绘制肿瘤生长曲线,测量各组肿瘤体积并计算抑瘤率,切除肿瘤组织进行瘤体组织常规病理学检查,分别用免疫组织化学及蛋白免疫印迹方法测定乏氧诱导因子(HIF-1α)的表达,TUNEL法检测肿瘤细胞凋亡。结果治疗第8天起,联合治疗组的瘤体积与对照组相比差异有统计学意义(P<0.05)。15d后,单纯放疗组、125I粒子植入组及联合治疗组的抑瘤率依次为45.9%、44.4%和69.4%,联合治疗组与其他各组比较差异有统计学意义(P<0.05),而单纯放疗组与12I5粒子植入组比较差异无统计学意义(P>0.05)。联合治疗组与其他各组相比HIF-1α改变均无统计学意义(P>0.05)。联合治疗组细胞凋亡明显。结论放疗联合125I粒子植入近距离治疗能显著抑制肿瘤的生长,较早诱导肿瘤细胞凋亡和退缩,但未抑制肿瘤细胞HIF-1α的表达,各治疗组均未出现急性毒性反应,治疗能耐受。

Objective To study the inhibitory effects of radiotherapy combined with 125I seed brachytherapy on the growth of transplanted human lung cancer cell line A549 in nude mice.Methods Model of transplanted human lung cancer cell line A549 was built on nude mice.Forty nude mice were randomly divided into four groups（with each group 10 mice） when tumor volume achieved （300±50）mm3.Control group （without any treatment）,radiotherapy group （given external exposure of 6 MV X rays for 10 Gy the first day）,125I seed brachytherapy group （125I seed with activity of 2775 MBq was embedded into the core of the tumor） and radiotherapy plus 125I seed group （combined group,125I seed with activity of 2775 MBq was embedded into the core of the tumor,which is given external exposure of 6 MV X rays for 10 Gy simultaneously the first day）.The tumor was observed for 15 days after treatment.Tumor growth curve was drawn and tumor volume was measured,and tumor inhibition rate was calculated too.At the same time,pathological examination was performed to the tumor tissue.The expression of HIF-1α was detected by immunohistochemistry and western blotting.The cell apoptosis was detected by TUNEL assay.Results Compared with the control group,the tumor volume of the combined treatment group was significantly smaller after 8 treatment days（P0.05）.After 15 treatment days,tumor inhibition rate of radiotherapy group,125I seed brachytherapy group and radiotherapy plus 125I seed group was 45.9%,44.4%,69.4% respectively,and the difference between the combined treatment group and other groups is significant （P0.05）,while the difference is not significant between the brachytherapy group and the 125I seed group （P0.05）.The difference of expression of HIF-1α between combined treatment group and other groups was not significant （P0.05）.Cell apoptosis is enhanced in combined treatment group.Conclusion Radiotherapy combined with 125I seed brachytherapy can inhibit the growth of tumor significantly,and can lead to apoptosis and recession of the tumor cell.But the treatment didn＇t inhibit the expression of HIF-1α.The treatment had well tolerance,with no acute toxic effects being found.