^(125)I粒子植入对人肝癌细胞裸鼠HepG2移植瘤的杀伤作用及其分子机制

Killing effect and molecular mechanism of ^(125)I seeds interstitial brachytherapy on human hepatocarcinoma cell HepG2 of transplanted tumor in nude mice

目的探讨不同剂量125I粒子组织间植入对人肝癌细胞裸鼠HepG2移植瘤的杀伤作用及其分子机制。方法构建20个人肝癌细胞HepG2的裸鼠移植瘤模型,随机分为4组,每组5只。3个治疗组分别接受18.5 MBq、29.6 MBq、37.0 MBq的125I粒子治疗,对照组不接受治疗。采用经皮肿瘤组织直接植入的方式分别将不同剂量125I粒子植入各治疗组小鼠的瘤体内,每只小鼠瘤体内植入1粒125I粒子。至治疗第28天处死小鼠,取肿瘤组织行常规病理学和免疫组织化学检查检测Bcl-2和Bax的表达情况。结果光镜下各治疗组肿瘤细胞呈不同程度凝固性坏死,周围广泛纤维化;对照组肿瘤细胞丰富,呈增殖样生长。免疫组织化学结果显示各治疗组中Bax的表达均高于对照组,并随125I粒子剂量的增加而逐渐增加;各治疗组中Bcl-2的表达及Bcl-2/Bax比值均低于对照组,并随125I粒子剂量的增加而逐渐减少。Bcl-2、Bax阳性率及Bcl-2/Bax比值在各治疗组与对照组间及各治疗组间的差异均有统计学意义(P均<0.05)。结论125I粒子组织间植入治疗可通过下调Bcl-2/Bax的比值促进裸鼠HepG2肝癌细胞凋亡,从而抑制肿瘤的生长;其诱导肝癌细胞凋亡的程度及抑制肿瘤生长的效果均在一定剂量范围内与剂量成正比。

Objective To investigate the killing effect and molecular mechanism of different doses of ^125I seed interstitial brachytherapy for human hepatoma HepG2 cells in nude mice transplanted tumor.Methods Twenty nude mice bearing human hepatoma HepG2 cells were randomly divided into 4 groups（each n=5） and given ^125I seed interstitial brachytherapy at different doses including 18.5 MBq ^125I,29.6 MBq ^125I,37.0 MBq^125I and 0（the control group）,respectively.125I seeds were percutaneously implanted into tumors,each mouse with 1 ^125I seed implanted.Twenty-eight days later,nude mice were sacrificed and routine pathological examination was performed.The expression of Bcl-2 and Bax was detected with immunohistochemical methods.Results Pathological examination showed serious coagulation necrosis of tumor cells surrounded by extensive fibrosis in all treatment groups,whereas rich tumor cells with proliferative growth were observed in the control group.Immunohistochemical analysis showed that the expression of Bax in all treatment group were higher than that in the control group,the expression of which was up-regulated with increasing doses of ^125I seed.The expression of Bcl-2 and the ratio of Bcl-2/Bax in all treatment groups were lower than those in the control group,the expression of which was down-regulated with increasing doses of ^125I seed.The expression of Bcl-2,Bax and the ratio of Bcl-2/Bax among treatment groups and control group had statistical difference（P〈0.05）,so as the difference among treatment groups（P〈0.05）.Conclusion 125I seed interstitial brachytherapy induces apoptosis in human hepatoma HepG2 cells by reducing the ratio of Bcl-2/Bax and thereby inhibits the growth of tumor in nude mice,and the extent positively correlates with dosage in a certain range.