TRAIL的抗肝细胞癌作用研究  

Antitumor effect of TRAIL in hepatocellular carcinoma

作　　者：何松青[1] 陈彦[1] 陈孝平[1] 赵永忠[1] 张万广[1] 王海平[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,武汉市430030

出　　处：《中华肝胆外科杂志》2003年第11期670-673,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：卫生部重点基金(2001)

摘　　要：目的 探讨TRAIL对HCC的治疗作用。方法 用不同浓度TRAIL处理肝癌细胞株HepG2、SMMC7721,观察经药物处理前后肿瘤细胞的凋亡发生率。采用分子克隆技术构建了真核表达质粒pIRES-EGFP-TRAIL,转染肝癌细胞株HepG2、SMMC7721细胞,观察其疗效。体内实验建立裸鼠肝癌模型,观察TRAIL的抑癌作用。结果 TRAIL(100 ng/ml)处理24 h,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QBC39凋亡发生率约50％。真核表达质粒TRAIL体外转染肝癌细胞后对肝癌细胞的生长无显著性的抑制作用。体内直接瘤体注射pIRES-EGFP-TRAIL可有效的导入TRAIL基因并获得高表达,但对裸鼠肝癌无明显抑制作用。结论 肝细胞癌对TRAIL诱导的凋亡有耐药现象,提示HCC中存在抑制TRAIL诱导凋亡的因素,单一的TRAIL治疗HCC疗效有限。Objective To investigate the therapeutic effect of TRAIL on hepatocellular carcinoma (HCC). Methods Cellular effects of TRAIL in promoting apoptosis in HCC cell lines HepG2 and SMMC-7721 (mutated by p53 gene) were analyzed after exposure to recombinant protein and transfec-lion with a cDNA expression plasmid. In vivo effects of TRAIL on tumor growth were determined u-sing HCC- model of HepG2 in nude mice. Results Recombinant TRAIL (100 ng/ml) alone was found to have a slight activity as it killed about 10% of HCC cells within 24 h compared to killing over 70% of Jurkate cells and about 50% of human cholangiocarcinoma cell line QBC939. The sensitivity to TRAIL did not correlate to the pattern of the status of p53. Transfection of cDNA of TRAIL also failed to induce extensive apoptosis in HCC lines. In vivo administration of TRAIL gene could not inhibit tumor grow in nude mice model. Conclusions HCC cells are insensitive to TRAIL-mediated apoptosis, suggesting the presence of mediators inhibiting the TRAIL-inducing apoptosis pathway in HCC. and limited therapeutic effect of TRAIL as a single agent on HCC.

关 键 词：TRAIL 肝细胞癌 细胞凋亡 治疗 肿瘤坏死因子相关凋亡诱导配体 

分 类 号：R735.7[医药卫生—肿瘤] R730.5[医药卫生—临床医学]