^125 I对乳腺肿瘤组织缺氧诱导因子-1α的作用及其机制

The effect of Iodine-125 interstitial brachytherapy of hypoxia inducible factor-1α in breast cancer and mechanism

目的探讨^125 I粒子对乳腺肿瘤组织缺氧诱导因子（HIF）-1α表达水平的影响及其分子生物学机制。方法建立人类乳腺癌MCF-7细胞株的裸鼠皮下移植瘤模型，将荷瘤鼠随机分两组（每组10只）：对照组：植入空载粒子和实验组^125 I粒子植入组（0．4mCi），瘤体长径8～10mm时植入^125 I粒子，粒子植入后当对照组瘤体平均长径15～20mm时，处死荷瘤小鼠，标本分别冻存和固定，用半定量逆转录．聚合酶链反应（RT-PCR）、蛋白免疫印记及免疫组织化学染色方法检测HIF-1α的mRNA及其蛋白表达水平。结果实验组中肿瘤组织及癌旁组织的HIF-1α的mRNA及其蛋白表达明显降低，与对照组比较差异有统计学意义[mRNA：q（肿瘤组织）=22．63，q（边缘组织）=19．53，P〈0．01；蛋白：q（肿瘤组织）=87．54，q（边缘组织）=80．39，P〈0．01；阳性细胞：q（肿瘤组织）=20．68，q（边缘组织）=16．47，P〈0．01]。两组正常组织中HIF—1α的表达变化不明显，差异无统计学意义（t=1．73，P〉0．05）。结论^125 I粒子抑制乳腺肿瘤组织促肿瘤血管生长因子HIF-1α mRNA及其蛋白水平的表达。

Objective To investigate the effect of the iodine-125 on the expression of hypoxia inducible factor-1αin breast cancer and the biological mechanism. Methods The animal models of the MCF-7 tumor were established first through the injection of the cells into nude mice subcutaneouly, followed by the implant of the iodine-125 granule of different groups into the tumor mass. The main method is resuscitation and serial subcultivation cell of MCF-7 tumor, and collect cell suspension（2 × 10^7 cell/ml） , each nude raice was injected cell suspension （0.5 ml） on hypodermic of right armpit or left shoulder. The animal were divided into two groups （one group contains 10 nude mice） ,control group ：to implant no-load seeds,non-iodine-125 radioelement （0 mCi） ;experiment group ：to implant iodine-125 seeds （0.4 mCi ）, to implant iodine-125 seeds when the length of tumor is 8-10 mm. The width and length of tumor,in order to calculate the volume ,were measured every two days till the length of tumor is 15 -20 mm, then kill the nude mice. To detect the mRNA and proteinum express level of HIF-1α by RT-PCR,Western blotting and immunohistochemistry. Results HIF-1α expression of tumor tissue was significantly decreased and that of paraneoplastic was decreased in experiment groups, there was significant difference compared with the con- trols [ mRNA ： q （ tumor tissue） = 22.63, q （ paraneoplastic tissue ） = 19.53, P 〈 0.01 ; proteinum ： q （ tumor tissue ） = 87.54, q （ paraneoplastic tissue ） = 80.39,P 〈 0.01 ; masculine cell ： q （ tumor tissue ） = 20.68, q （paraneoplastic tissue） = 16.47 ,P 〈 0.01 ]. There was no significant difference among the two groups in expression of HIF-1α of normal（t = 1.73 ,P 〉 0.05）. Conclusion Iodine-125 seeds restrain the express of facilitative tumor vessel growth gene HIF-1α in breast tumor tissue so that to restrain growth of tumor.