TRAIL、Ki-67蛋白在人骨肉瘤中表达及其与肿瘤细胞增殖和凋亡的关系

摘要

Objective: To investigate the expression and distribution of TRAIL and Ki-67 proteins, as well as the relationship between these proteins and the proliferation and apoptosis of human osteosarcoma cells.Methods: Immunohistochemistry was used to evaluate the distribution of TRAIL and Ki-67 proteins in groups of patients with either osteosarcoma or osteochondroma.Apoptosis was detected by In Situ Terminal Deoxy-nucleotide Transferase Labeling (TUNEL), and apoptotic cells could be seen when FITC labeling was examined with confocal laser scanning microscopy.The proliferation index and apoptosis index were then calculated.Results: The positive expression of TRAIL protein in osteosarcoma was significantly lower than that in osteochondroma ( t = -5.51, P ＜ 0.05), while the positive expression of Ki-67 protein was significantly higher in the osteosarcoma group than in the osteochondroma group ( t = 17.69, P ＜ 0.05).There was a significant negative correlation between TRAIL and Ki-67 protein expression in osteosarcoma ( r = -0.8444, P ＜ 0.01).The apoptosis index (AI) was lower in the osteosarcoma group than in the osteochondroma group ( P ＜ 0.01).The proliferation index (PI) was higher in the osteosarcoma group than in the osteochondroma group ( P ＜ 0.01).There was a negative correlation between Ki-67 protein expression and the AI ( r = -0.5622, P ＜ 0.01).There was a positive correlation between TRAIL protein expression and the AI ( r = 0.6350, P ＜ 0.01) and a negative correlation between TRAIL protein expression and the PI ( r = -0.5530, P ＜ 0.01).Conclusion: TRAIL protein is important in inducing apoptosis of osteosarcoma cells and it takes part in the process of cellular apoptosis.Ki-67 protein plays an important role in the proliferation and apoptosis of osteosarcoma.The significant overexpression of Ki-67 and underexpression of TRAIL protein in osteosarcoma may be closely related to the occurrence and development of osteosarcoma.Lowering Ki-67 overexpression and raising TRAIL underexpression may increase apoptosis in osteosarcoma cells.%目的:通过观察TRAIL、Ki-67在人骨肉瘤组织中的表达规律及其相互关系,探讨二者与骨肉瘤细胞增殖、凋亡的相关性.方法:用免疫组织化学方化法检测TRAIL、Ki-67蛋白在骨肉瘤及骨软骨瘤中的表达,用TUNEL方法通过激光扫描共聚焦显微镜检测骨肉瘤及骨软骨瘤组织中的细胞凋亡分布情况并计算增殖和凋亡指数.结果:骨肉瘤组织TRAIL蛋白表达强度低于骨软骨瘤(t=-5.51,P＜0.05);而Ki-67蛋白表达高于骨软骨瘤(t=17.69,P＜0.05).TRAIL和Ki-67在骨肉瘤中的表达呈负相关(r=-0.8444,P＜0.01).骨肉瘤中细胞凋亡指数(AI)显著低于骨软骨瘤(P＜0.01);而增殖指数(PI)显著高于骨软骨瘤(P＜0.01).骨肉瘤中Ki-67蛋白表达与细胞凋亡指数之间呈负相关(r=-0.562 2,P＜0.01);而TRAIL蛋白表达与细胞凋亡指数呈正相关(r=0.6350,19<0.01),而与增殖指数呈负相关(r=-0.553 0,19<0.01).结论:TRAIL参与细胞凋亡的调控,可能是诱导骨肉瘤细胞凋亡的分子基础之一;Ki-67在肿瘤细胞的增殖与凋亡中具有重要作用,骨肉瘤组织中Ki-67明显过表达,而TRAIL蛋白表达明显下调,表明两者在骨肉瘤的发生、发展中起拮抗作用.如能抑制Ki-67的表达,促进TRAIL的表达,有可能提高骨肉瘤细胞的凋亡敏感性.