Expression and biological significance of c-FLIP in human hepatocellular carcinomas.
Expression and biological significance of c-FLIP in human hepatocellular carcinomas.
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c-FLIP在人肝细胞癌中的表达及生物学意义
DOI：
10.1186/1756-9966-28-24
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发表时间：
2009-02-20
期刊：
影响因子：
--
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Du X;Bao G;He X;Zhao H;Yu F;Qiao Q;Lu J;Ma Q
背景c-flip可以被认为是一种肿瘤进展因子，因为它具有抗细胞凋亡的功能。本研究旨在通过siRNA对7721细胞c-Flip表达的特异性抑制，探讨c-Flip在人肝癌组织中的表达及其与药物诱导细胞凋亡的关系。方法采用免疫组织化学方法对86例肝癌组织及57例癌旁组织中c-Flip的表达进行定量。对肝癌患者进行了肿瘤复发的随访。然后，在7721肝癌细胞中用特异的siRNA沉默c-flip基因。采用逆转录聚合酶链式反应、Western Blot和免疫细胞化学方法检测c-flip蛋白的表达。结果83.72%(72/86)的人肝细胞癌组织、14.81%(4/27)的肝硬变组织、11.11%(2/18)的肝血管瘤组织呈阳性表达，而正常肝组织中未见阳性表达。C-FLIP在肝细胞癌中的过度表达(超过50%)对无复发生存率有不利影响。通过siRNA沉默c-flip基因，可显著下调7721肝癌细胞中c-flip的mRNA和蛋白表达。阿霉素对细胞增殖有明显的抑制作用，可诱导更多的细胞凋亡。结论c-FLIP在人肝细胞癌中广泛表达，其过表达提示肝癌的无复发生存概率较低。C-flip基因的特异性沉默可以明显上调药物诱导的肝癌细胞的凋亡，可能对人肝癌的治疗有潜在的作用。
Backgroundc-FLIP can be considered as a tumor-progression factor in regard to its anti-apoptotic functions. In the present study, we intended to investigate the expression of c-FLIP in human HCC tissues, and its relation with drug-induced cell apoptosis through the specific inhibition of c-FLIP expression by siRNA in 7721 cells.Methodsc-FLIP expression was quantified immunohistochemically in HCC tissues(eighty-six cases), and corresponding noncancerous tissues (fifty-seven cases). Patients with HCC were followed up for cancer recurrence. Then, the c-FLIP gene was silenced with specific siRNA in 7721 HCC cells. c-FLIP expression was detected by RT-PCR, Western Blot and immunocytochemical staining. The cellular viability and cell apoptosis were assayedin vitrowith cells treated with doxorubicin.ResultsPositive immunostaining was detected for c-FLIP in 83.72% (72/86) human HCC tissues, 14.81% (4/27) hepatic cirrhosis, 11.11% (2/18) hepatic hemangioma tissues, and absent in normal hepatic tissues. The overexpression(more than 50%) of c-FLIP in HCC adversely affected the recurrence-free survival. Through c-FLIP gene silencing with siRNA, the expressions of c-FLIP mRNA and protein were remarkably down-regulated in 7721 HCC cells. And doxorubicin showed apparent inhibition on cell proliferations, and induced more apoptosis.ConclusionThese results indicate that c-FLIP is frequently expressed in human HCCs, and its overexpression implied a lesser probability of recurrence-free survival. The specific silencing of c-FLIP gene can apparently up-regulate drug-induced HCC cell apoptosis, and may have therapeutic potential for the treatment of human HCC.
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影响因子：
7.2
作者：
Flahaut, M;Mühlethaler-Mottet, A;Gross, N
通讯作者：
Gross, N
影响因子：
11.5
作者：
Mezzanzanica, D;Balladore, E;Canevari, S
通讯作者：
Canevari, S
影响因子：
8
作者：
Longley, DB;Wilson, TR;Johnston, PG
通讯作者：
Johnston, PG
影响因子：
6.4
作者：
Korkolopoulou, P.;Saetta, A. A.;Patsouris, E.
通讯作者：
Patsouris, E.
影响因子：
64.8
作者：
Irmler, M;Thome, M;Tschopp, J
通讯作者：
Tschopp, J