Expression of somatostatin receptors in normal and cirrhotic human liver and in hepatocellular carcinoma
Expression of somatostatin receptors in normal and cirrhotic human liver and in hepatocellular carcinoma
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DOI：
10.1136/gut.2003.036053
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发表时间：
2004-08-01
期刊：
影响因子：
24.5
通讯作者：
Geerts, A
中科院分区：
文献类型：
--
作者：
Reynaert, H;Rombouts, K;Geerts, A
背景：生长抑素类似物已被用于治疗晚期肝细胞癌 (HCC)，但结果相互矛盾。本研究旨在探讨生长抑素受体（SSTR）亚型在人肝脏中的表达，并探讨选择性SSTR激动剂对肝癌细胞（HepG2、HuH7）和肝星状细胞（HSC）增殖、凋亡和迁移的影响。方法：采用免疫组化和逆转录聚合酶链反应检测细胞系、正常和肝硬化肝脏以及HCC中SSTR的表达。分别通过5-溴-2'脱氧尿苷和TUNEL方法评估SSTR激动剂对肿瘤细胞和HSC增殖和凋亡的影响。使用Boyden小室研究SSTR激动剂对迁移的影响。结果：在正常肝脏中，肝细胞和HSC对所有五种SSTR均为阴性。肝硬化肝和 HCC 以及培养的肝癌细胞和 HSC 在蛋白质和 mRNA 水平上均表达所有五种 SSTR，但不与 SSTR3 发生免疫反应的 HuH7 细胞除外。没有一种激动剂影响增殖或凋亡。然而，与未处理的细胞相比，SSTR1 激动剂 L-797,591 将 HepG2、HuH7 和 HSC 的迁移显着降低，分别降至 88 (7)% (p< 0.05)、83 (11)% (p< 0.05) 和 67 (13)% (p< 0.01)。 结论：肝硬化肝脏和 HCC 表达 SSTR。尽管本研究中使用的生长抑素类似物不影响增殖和凋亡，但刺激 SSTR1 可能通过减少肝癌细胞和/或 HSC 的迁移来降低 HCC 的侵袭性。评估生长抑素类似物治疗 HCC 的临床试验应考虑这些发现。
Background: Somatostatin analogues have been used with conflicting results to treat advanced hepatocellular carcinoma (HCC). The aim of this study was to investigate expression of somatostatin receptor ( SSTR) subtypes in human liver, and to examine the effect of selective SSTR agonists on proliferation, apoptosis, and migration of hepatoma cells (HepG2, HuH7) and hepatic stellate cells (HSCs).Methods: Expression of SSTRs in cell lines, normal and cirrhotic liver, and HCC was examined by immunohistochemistry and reverse transcription-polymerase chain reaction. Effects of SSTR agonists on proliferation and apoptosis of tumour cells and HSCs were assessed by the 5-bromo-2' deoxyuridine and TUNEL methods, respectively. The influence of SSTR agonists on migration was investigated using Boyden chambers.Results: In normal liver, both hepatocytes and HSCs were negative for all five SSTRs. Cirrhotic liver and HCC as well as cultured hepatoma cells and HSCs expressed all five SSTRs, both at the protein and mRNA levels, except for HuH7 cells which did not immunoreact with SSTR3. None of the agonists influenced proliferation or apoptosis. However, compared with untreated cells, L-797,591, an SSTR1 agonist, reduced migration of HepG2, HuH7, and HSCs significantly to 88 (7)% ( p< 0.05), 83 (11)% (p< 0.05), and 67 (13)% ( p< 0.01), respectively.Conclusions: Cirrhotic liver and HCC express SSTRs. Although the somatostatin analogues used in this study did not affect proliferation and apoptosis, stimulation of SSTR1 may decrease invasiveness of HCC by reducing migration of hepatoma cells and/or HSCs. Clinical trials evaluating somatostatin analogues for the treatment of HCC should take these findings into account.