不同活度^(125)I粒子植入抑制兔VX2肝癌机制研究

The inhibition effect of interstitial brachytherapy with different radioactivity ^(125)I seeds on liver VX2 tumor in experimental rabbits: study of its mechanism

目的探讨125I粒子组织间植入诱导肝癌细胞凋亡的机制。比较不同活度125I粒子组织间植入诱导肿瘤细胞凋亡、抑制肿瘤细胞增殖的作用强度。方法将24只兔VX2肝癌模型随机分为3组,分别植入不同初始活度的125I粒子:0 m Ci组(对照组,n=8)、0.7 m Ci组(n=8)及1.0 m Ci组(n=8)。5周后处死实验兔,取出肿瘤病灶,检测125I粒子对肿瘤细胞凋亡、肿瘤生长相关因子表达的影响及caspase-3活性改变。结果不同初始活度125I粒子均可使肿瘤细胞凋亡率上升,Bcl-2、VEGF表达下调,Bax表达上调,1.0 m Ci125I粒子组作用均更加明显(P<0.05)。不同初始活度125I粒子可增加肿瘤组织中caspase-3活性,两治疗组间差异无明显统计学意义(P>0.05)。结论 125I粒子植入后不仅通过诱导肿瘤细胞凋亡抑制肿瘤生长、增殖,还影响凋亡相关基因及编码蛋白表达,抑制肿瘤细胞新生血管生成。

Objective To explore the mechanism of 125I seed interstitial implantation-induced apoptosis of liver VX2 tumor cells in experimental rabbits, and to compare the effects of different radioactivity 125I seeds on the apoptosis and on the proliferation of tumor cells. Methods A total of 24 rabbit models with VX2 liver cancer were randomly and equally divided into 3 groups, and 125I seeds with different initial radioactivity were separately implanted into the rabbits of the three groups. 125I seeds of 0 mCi radioactivity were used in the control group （n=8）, 125I seeds of 0.7 mCi radioactivity were used in the 0.7 mCi group （n=8） and 125I seeds of 1.0 mCi radioactivity were used in the 1.0 mCi group （n=8）. The experimental rabbits were sacrificed at 5 weeks after the implantation; the tumor lesions were removed, and the effects of 125I seeds on the apoptosis and proliferation of tumor cells were determined. The tumor cell apoptosis rate, tumor growth-related factors, tumor growth factor expression protein and the influence of caspase-3 activity were evaluated. Results Regardless of their initial radioactivity, all the 125I seeds could make the tumor cell apoptosis rate increased, make Bcl-2 and VEGF expression level decreased, and make Bax expression increased, which were more obvious in 1.0 mCi group （P〈0.05）. The 125I seeds could increase the activity of caspase-3 within tumor tissue, but the difference between the 0.7 mCi group and the 1.0 mCi group was not significant （P〉0.05）. Conclusion The implanted 125I seeds can not only inhibit tumor’s growth through inducing apoptosis of tumor cells, but also inhibit tumor’s angiogenesis through influencing the expression of apoptosis-related gene and coding protein.