放射性^(125)I粒子对人肺癌移植瘤小鼠的抑瘤作用及对细胞凋亡的作用研究

Study on the Antitumor Effect of Radioactive^(125)I Seed on Human Lung Cancer Transplanted Tumor Mice and the Effect on Apoptosis

目的探讨放射性^(125)I粒子对人肺癌移植瘤小鼠肿瘤的抑制作用及对细胞凋亡的影响。方法将肺癌A549细胞种植入30只小鼠背部皮下,接种成功后将30只小鼠随机分为模型组、空白对照组和观察组。6天后,将1枚空白粒子植入空白对照组小鼠移植瘤内,观察组小鼠移植瘤内植入^(125)I粒子1枚,模型组小鼠移植瘤内不植入任何粒子。28 d后测定移植瘤体积并计算抑瘤率、HE染色观察瘤组织病理学变化、免疫组织化学法检测细胞增殖核抗原(Ki67)表达计算细胞增殖指数、TUNEL染色检测细胞凋亡情况以及蛋白印迹法(WB法)检测半胱氨酸天冬氨酸蛋白酶3(cleaved caspase-3)、B淋巴细胞瘤-2(Bcl-2)和Bcl-2相关X蛋白(Bax)相对表达量。结果模型组和空白对照组细胞结构完整、无坏死或少量坏死,观察组细胞结构被破坏、出现大量坏死、坏死区周围细胞分布不均匀且细胞间隙增宽。与模型组和空白对照组比较,观察组小鼠肿瘤体积减小、细胞凋亡指数及cleaved caspase-3和Bax表达升高,细胞增殖指数及Bcl-2表达降低(P<0.05);与空白对照组比较,观察组抑瘤率升高(P<0.05)。结论^(125)I粒子可抑制肺移植瘤生长,诱导瘤细胞凋亡,可能是通过调控Bcl-2/Bax/caspase-3凋亡相关蛋白发挥作用。

Objective To investigate the inhibitory effect of radioactive^(125)I particles on tumor and apoptosis of human lung cancer transplanted tumor mice.Methods Lung cancer A549 cells were implanted subcutaneously into the back of 30 mice.After successful inoculation,30 mice were randomly divided into model group,blank control group and observation group.6 days later,1 blank particle was implanted into the transplanted tumor of mice in the blank control group,1^(125)I seed was implanted into the transplanted tumor of mice in the observation group,and no seed was implanted into the transplanted tumor of mice in the model group.After 28 days,tumor volume was measured and tumor inhibition rate was calculated,tumor histopathological changes were observed by HE staining,cell proliferative nuclear antigen(Ki67)expression was detected by immunohistochemistry and cell proliferation index was calculated,cell apoptosis was detected by TUNEL staining,and cysteine aspartic protease 3(cleaved)was detected by western blot(WB)caspase-3),B-lymphoblastoma-2(Bcl-2),and Bcl-2 associated X protein(Bax).Results The cell structure of the model group and the blank control group was complete with no or a little necrosis,while the cell structure of the observation group was destroyed with a large amount of necrosis,uneven distribution of cells around the necrotic area and widening of the cell space.Compared with model group and blank control group,tumor volume decreased,apoptosis index,cleaved caspase-3 and Bax expression increased,cell proliferation index and Bcl-2 expression decreased in observation group(P<0.05).Compared with blank control group,the inhibitory rate in observation group was increased(P<0.05).Conclusion Radioactive^(125)I seeds inhibited the growth of lung transplanted tumor and promoted the apoptosis of tumor cells,which may play a role through the regulation of apoptosis-related proteins.