可溶性肿瘤坏死因子相关凋亡诱导配体诱导肝癌细胞凋亡的研究

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目的 研究肿瘤坏死因子相关凋亡诱导配体 (TRAIL)对肝癌细胞凋亡的诱导作用。方法 采用原位杂交方法检测肝癌组织、肝癌细胞株以及正常肝组织中TRAILR的表达。采用不同浓度TRAIL蛋白处理肝癌细胞株HepG2和SMMC772 1,应用流式细胞仪和原位末端标记 ,观察经药物处理前后该细胞株的凋亡发生率。结果  6 0例肝癌组织及 2 0例正常肝组织均表达死亡受体DR5和DR4 ,但肝癌组织DR表达量显著强于正常肝组织。 5 4例 (90 .0 % )肝癌组织不表达诱捕受体DcR1,2 5例 (4 1.7% )肝癌组织不表达DcR2 ,而 2 0例正常肝组织均表达DcR。肝癌组织中DR的高表达及DcR的低表达 ,不同于正常肝组织中DR的低表达及DcR的高表达 ,两者间差异有显著性。两种肝癌细胞株中均可检测到DR5、DR4、DcR2的表达 ,但DcR1表达缺失。肝癌组织中DR的表达与肿瘤的分化、肿瘤分期有关 ,低分化的肿瘤DR表达减少 (P <0 .0 1) ,Ⅲ、Ⅳ期肿瘤DR表达显著低于Ⅰ、Ⅱ期 (P <0 .0 5 )。DR表达与患者的性别、年龄、HBsAg阳性与否、AFP水平、肿瘤大小以及是否转移无关。经TRAIL(10 0ng/ml)处理 2 4h ,肝癌细胞凋亡发生率约 10 % ,而Jurkat细胞凋亡率达 70 %以上 ,胆管癌细胞QBC939凋亡发生率约 5 0 %。结论 肝细胞肝癌普遍存在TRAILR的表达 ,并存在受体类型? Objective To study the induction of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on hepatocellular carcinoma cell apoptosis. Methods The expression of TRAILR in hepatocellular carcinoma, hepatocellular carcinoma cell lines and normal liver tissues was detected by in situ hybridization. The hepatoma cell lines HepG2 and SMMC772 were treated with different concentrations of TRAIL 1. The apoptosis rate of the cell lines was observed by flow cytometry and in situ end-labeling. Results The death receptor DR5 and DR4 were expressed in 60 liver cancer tissues and 20 normal liver tissues, but the expression of DR in liver cancer tissues was significantly higher than that in normal liver tissues. Fifty-four (90.0%) HCCs did not express DcR1, 25 (4 1.7%) HCC did not express DcR2, while 20 normal liver tissues expressed DcR. The high expression of DR and the low expression of DcR in hepatocellular carcinoma are different from the low expression of DR and the high expression of DcR in normal liver tissue, the difference between them is significant. DR5, DR4 and DcR2 were detected in both hepatocellular carcinoma cell lines, but the expression of DcR1 was absent. The expression of DR in hepatocellular carcinoma was correlated with tumor differentiation and tumor staging. The expression of DR in poorly differentiated tumor was decreased (P <0.01). The expression of DR in stage Ⅲ and Ⅳ was significantly lower than that in stage Ⅰ and Ⅱ (P <0. 0 5). DR expression and the patient’s gender, age, HBsAg-positive or not, AFP level, tumor size and whether the transfer has nothing to do. The apoptosis rate of HCC cells was about 10% after treated with TRAIL (10 0ng / ml) for 24 hours, while the apoptosis rate of Jurkat cells was above 70%, and the apoptosis rate of QBC939 cells was about 50%. Conclusion The prevalence of TRAILR in hepatocellular carcinoma and the presence of receptor type?
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