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可溶性肿瘤坏死因子相关凋亡诱导配体在人肝细胞癌中的抗肿瘤作用

[Antitumor effects of soluble TRAIL in human hepatocellular carcinoma].

作者信息

He Song-qing, Chen Yan, Chen Xiao-ping, Zhang Wan-guang, Wang Hai-ping, Zhao Yong-zhong, Wang Shao-fa

机构信息

Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2003 Mar;25(2):116-9.

Abstract

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.

摘要

目的

探讨可溶性肿瘤坏死因子相关凋亡诱导配体(sTRAIL)在肝细胞癌(HCC)中的治疗潜力。

方法

采用原位杂交法检测60例手术切除的肝细胞癌组织、20例良性肿瘤边缘正常肝组织及2种肝癌细胞系(HepG2和SMMC-7721)中TRAILR的表达。分析患者的临床资料,以及不同浓度重组蛋白作用后sTRAIL对肝癌细胞系HepG2和SMMC-7721(p53基因发生突变)促凋亡的细胞效应。

结果

肝癌组织中高死亡受体(DR)表达和低诱捕受体(DcR)表达,与正常肝组织中低DR表达和高DcR表达存在统计学差异。两种细胞系均表达DR5、DR4和DcR2,但不表达DcR1。DR的表达与肝癌分化密切相关,在低分化中表达较弱。32例Ⅲ-Ⅳ级DR表达阳性率显著低于28例Ⅰ-Ⅱ级(P<0.05)。单独重组TRAIL 24小时后,肝癌细胞、Jurkat细胞和人胆管癌细胞系QBC939的细胞凋亡率分别为10%、70%和50%。

结论

TRAILR在肝癌中普遍表达,存在不同的受体类型。肝癌对TRAIL介导的凋亡具有抗性。单独使用TRAIL治疗对诱导HepG2和SMMC-7721肝癌细胞系凋亡的作用有限。

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