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  

Antitumor effects of soluble TRAIL in human hepatocellular carcinoma

作　　者：何松青[1] 陈彦[1] 陈孝平[1] 张万广[1] 王海平[1] 赵永忠[1] 王少发[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝胆胰研究所,武汉430030

出　　处：《中华肿瘤杂志》2003年第2期116-119,共4页Chinese Journal of Oncology

基　　金：卫生部临床学科重点项目 ( 2 0 0 1)

摘　　要：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 investigate therapeutic potential of soluble TRAIL (sTRAIL) in hepatocellular carcinoma (HCC). Methods Expression of TRAILR was determined by in situ hybridization in 60 samples of resected hepatocellular carcinoma, 20 samples of normal liver tissue near the margin of benign tumor and 2 HCC cell lines of HepG2 and SMMC 7721. The clinical data of the patients were analyzed as well as cellular effects of sTRAIL in promoting apoptosis on HCC cell lines HepG2 and SMMC 7721 (p53 gene mutated) after exposure to different concentrations of recombinant protein. Results High death receptor (DR) expression and low DcR expression in HCC tissue differed from low DR expression and high DcR expression in the normal hepatic tissue with statistical significance. DR5, DR4, and DcR2 but not DcR1 were expressed in both cell lines. The expression of DR was closely correlated with HCC differentiation, with the weak expression in poor differentiation. The positive rate of DR expression in 32 cases of grade Ⅲ Ⅳ was significantly lower than that in 28 cases of grade Ⅰ Ⅱ ( P < 0.05 ). Cell apoptosis rates were 10%, 70% and 50% of HCC cells, Jurkat cells and human cholangiocarcinoma cell line QBC939 24 h after recombinant of TRAIL alone. Conclusion TRAILR expression is prevalent in HCC, with different receptor types existing. HCC is resistant to TRAIL mediated apoptosis. The treatment of TRAIL alone only has a limited effect on inducing apoptosis on HCC cell lines of HepG2 and SMMC 7721.

关 键 词：肝癌 可溶性肿瘤坏死因子相关凋亡诱导配体 细胞凋亡 HEPG2 SMMC772 HCC 

分 类 号：R735.7[医药卫生—肿瘤]