Hypoxia and cytokines regulate carbonic anhydrase 9 expression in hepatocellular carcinoma cells in vitro
Hypoxia and cytokines regulate carbonic anhydrase 9 expression in hepatocellular carcinoma cells in vitro
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DOI：
10.5306/wjco.v3.i6.82
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发表时间：
2012-06-10
影响因子：
2.8
通讯作者：
Said, Harun M.
中科院分区：
文献类型：
--
作者：
Kockar, Feray;Yildrim, Hatice;Said, Harun M.
目的：研究碳酸酐酶（CA） 9在人肝癌细胞中的表达。方法：研究不同平行方法暴露的Hep3B细胞CA9蛋白、CA9 mRNA和缺氧诱导因子-1 α (HIF-1 α)蛋白水平。在其中一种方法中，HCC细胞暴露于极端体外缺氧（24小时0.1% O-2），没有或有白细胞介素(IL)-1、IL-6、肿瘤坏死因子- α (tnf - α)和转化生长因子- β (TGF-ss)刺激，相同的缺氧暴露时间，或暴露于缺氧缺氧条件下，没有或有细胞因子刺激。结果：所分析的肿瘤细胞系在长时间严重缺氧的情况下表现出强烈的缺氧CA9 mRNA表达模式，具有细胞系特异性模式，并且在严重缺氧的情况下CA9蛋白被显著诱导。这些结果与相同氧合条件下HIF-1 α蛋白的表达趋势与CA9蛋白表达实验系列的结果相似。在常氧条件下，持续刺激细胞因子IL-1、IL-6、tnf - α和TGF-ss可显著提高碳酸酐酶9蛋白和mRNA的表达水平，几乎是缺氧条件下CA9 mRNA、CA9和HIF-1 α蛋白表达水平的两倍。这些实验结果表明，缺氧是HCC中CA9表达的正向调节因子，并且在常氧和缺氧条件下，IL-1、IL-6、tnf - α和TGF-ss这四种信号转导途径都对CA9表达有正向影响。结论：这些发现可能在设计涉及缺氧诱导或细胞因子刺激表达的抗癌治疗方法时被考虑。此外，他们提供
AIM: To study the expression of carbonic anhydrase (CA) 9 in human hepatocellular carcinoma (HCC) cells.METHODS: We studied CA9 protein, CA9 mRNA and hypoxia-inducible factor-1 alpha (HIF-1 alpha)protein levels in Hep3B cells exposed in different parallel approaches. In one of these approaches, HCC cells were exposed to extreme in vitro hypoxia (24 h 0.1% O-2) without or with interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-ss) stimulation for the same hypoxic exposure time or exposed to normoxic oxygenation conditions without or with cytokine stimulation.RESULTS: The tumour cell line analysed showed a strong hypoxic CA9 mRNA expression pattern in response to prolonged severe hypoxia with cell-line specific patterns and a marked induction of CA9 protein in response to severe hypoxia. These results were paralleled by the results for HIF-1 alpha protein under identical oxygenation conditions with a similar expression tendency to that displayed during the CA9 protein expression experimental series. Continuous stimulation with the cytokines, IL-1, IL-6, TNF-alpha and TGF-ss, under normoxic conditions significantly increased the carbonic anhydrase 9 expression level at both the protein and mRNA level, almost doubling the CA9 mRNA and CA9 and HIF-1 alpha protein expression levels found under hypoxia. The findings from these experiments indicated that hypoxia is a positive regulator of CA9 expression in HCC, and the four signal transduction pathways, IL-1, IL-6, TNF-alpha and TGF-ss, positively influence CA9 expression under both normoxic and hypoxic conditions.CONCLUSION: These findings may potentially be considered in the design of anti-cancer therapeutic approaches involving hypoxia-induced or cytokine stimulatory effects on expression. In addition, they provide