The inhibitory effect of p75 neurotrophin receptor on growth of human hepatocellular carcinoma cells
The inhibitory effect of p75 neurotrophin receptor on growth of human hepatocellular carcinoma cells
复制标题
p75神经营养素受体对人肝癌细胞生长的抑制作用。
DOI：
10.1016/j.canlet.2008.03.038
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发表时间：
2008-09-08
期刊：
影响因子：
9.7
通讯作者：
Fan Daiming
中科院分区：
文献类型：
--
作者：
He Yuanlong;Jin Haifeng;Fan Daiming
p75神经营养因子受体（p75NTR）是TNF受体超家族成员之一，是目前研究的热点。迄今为止，其在肝细胞癌中的作用和功能尚未完全阐明。在本研究中，我们研究了p75NTR在肝细胞癌中的表达及其改变对肿瘤生长的影响。我们发现p75NTR在158例肝细胞癌组织中的表达与邻近的非癌组织相比显著降低，并且在各种人肝细胞癌细胞系中的表达也显著降低。通过特异性siRNA下调p75NTR可促进正常肝细胞株的生长，而上调p75NTR在体外可抑制肝癌细胞株的生长，并通过诱导细胞周期阻滞在体内显著抑制肿瘤生长。此外，我们发现上调p75NTR可下调cyclin A、cyclin d1、cyclin E、cdk2、p-Rb和PCNA的表达，上调Rb的表达。相反，当p75NTR被特异性siRNA下调时，结果相反。因此，我们提供了证据，证明p75NTR是一种潜在的肿瘤抑制因子，可能作为肝细胞癌的治疗靶点。2008爱思唯尔爱尔兰有限公司版权所有。
p75 neurotrophin receptor (p75NTR), a member of the TNF receptor superfamily, is a focus for study at present. Up to now, its role and functions in hepatocellular carcinoma were not fully elucidated. In this study, we investigated the expression of p75NTR in hepatocellular carcinoma and the impact of its alteration on tumor growth. We found that the expression of p75NTR was decreased significantly in 158 cases of hepatocellular carcinoma tissues as compared with their adjacent noncancerous counterparts, and its expression was also significantly decreased in various human hepatocellular carcinoma cell lines. Down-regulating p75NTR by specific siRNA promoted the growth of normal liver cell lines, whereas up-regulating p75NTR inhibited the growth of hepatocellular carcinoma cell lines in vitro and caused dramatic attenuation of tumor growth in vivo by induction of cell cycle arrest. Furthermore, we found that up-regulating p75NTR could down-regulate the expression of cyclin A, cyclin D I, cyclin E, cdk2, p-Rb and PCNA, but up-regulate the expression of Rb. Conversely, the results were inverse when p75NTR was down-regulated by specific siRNA. Therefore, we provided the evidence that p75NTR was a potential tumor suppressor and might be used as a therapeutic target for hepatocellular carcinoma. (C) 2008 Elsevier Ireland Ltd. All rights reserved.