^125I粒子组织间植入治疗荷瘤裸鼠移植性肝癌

^(125)I interstitial brachytherapy in the treatment of transplanted hepatoma in nuce mice

目的:研究125I粒子植入对小鼠皮下肝癌移植瘤的治疗效果。方法:22只BALB/c小鼠皮下移植肿瘤细胞H22建瘤,荷瘤鼠随机分为125I粒子治疗组和对照组,治疗组12只,对照组10只。连续观察25d小鼠存活情况,测量肿瘤大小。25d后处死小鼠,制作肿瘤组织标本,进行常规病理学检查。免疫组织化学法检测增殖细胞核抗原(proliferation cell nuclear antigen,PCNA)、Fas(factor assciated suicide)及微血管密度(microvessel density,MVD)的表达。结果:25d后,125I粒子治疗组和对照组小鼠存活率分别为83.3%和50.0%;平均肿瘤体积分别为(381.5±72.64)mm3和(5620.9±969.8)mm3,治疗组和对照组比较,差异有统计学意义(P<0.01);治疗组病理切片显示肿瘤细胞大片凝固样坏死区和条梭状的纤维组织增生,对照组肿瘤细胞呈增殖样生长;免疫组织化学结果显示治疗组肿瘤细胞凋亡明显,与对照组比差异有统计学意义。结论:125I粒子组织间植入持续照射可以直接杀死肿瘤细胞,也可以抑制肿瘤细胞增殖,诱导肿瘤细胞凋亡,从而抑制肿瘤生长。

Objective：To investigate the therapeutic effect of ^125I seeds interstitial brachytherapy on the subcutaneously implanted hepatocellular carcinoma in mice. Methods：H 22 cells （2×10^7/0.2 mL） were transplanted subcutaneously in the right lateral back of 22 BALB/c nude mice. The xenografted tumor model was established after 15 d. The mean diameter of tumor was 12 mm. The tumor-beared nude mice were divided into a ^125I seeds interstitial brachytherapy group （n=12） and a control group （n=10）. The survival rates of mice and the tumor size were measured. After 25 d, nude mice were executed and pathological examination was performed. The expression of the proliferation cell nuclear antigen （PCNA） and factor-associated suicide （FAS） were determined by immunohistoche-mical methods. The ratio of microvascular density （MVD） in the two groups was calculated. Results：At d 25 after seeds implantation, the survival rates were 83.3% and 50% and the mean tumor volumes were （381.5±72.64）mm^3 and （5 620.9±969.8）mm^3 in the treatment group and control group, respectively. The difference was significant between the two groups （P〈0.01）. Histological analysis revealed coagulative necrosis, inflammatory cell invasion and fibrosis in the surrounding area of the implantation site of radioactive seeds, whereas in the surrounding area of the dummy seeds only slight fibrosis and edema were observed, with proliferation of tumor cells. Immunohistochemistry analysis showed that there was apparent apoptosis of tumor cells in ^125I seeds implantation group. There was significant difference between the treatment group and the control group. Conclusion：^125I seed interstitial brachytherapy inhibites the growth of tumor by directly killing tumor cells, inhibiting its proliferation and inducing apoptosis.