摘要： 目的：观察低氧与人舌鳞状细胞癌SCC-6细胞中HIF-1α、VEGF表达的相关性，曲古抑菌素A（TSA）对其表达的抑制作用，初步探讨其作用机制。方法：体外培养的舌鳞状细胞癌SCC-6细胞，经不同作用时间去铁胺处理，模拟低氧条件培养后，RT-PCR检测HIF-1α、VEGF的mRNA表达，Western Blot检测其蛋白表达；模拟低氧条件下，不同浓度、时间梯度TSA处理SCC-6细胞后，分别检测HIF-1α、VEGF的mRNA及蛋白表达。结果：①低氧下SCC-6细胞HIF-1α蛋白表达增加，但其mRNA的表达不受影响；作为HIF-1α下游基因的VEGF的mRNA和蛋白表达，随HIF-1α蛋白表达增加而增加；②低氧下，TSA可抑制HIF-1α的蛋白表达及VEGF的mRNA和蛋白表达，并呈量效和时效关系，但HIF-1α的mRNA表达不受影响；③HIF-1α的调节在蛋白水平。结论：体外条件下，模拟低氧可诱导舌鳞状细胞癌SCC-6细胞中HIF-1α蛋白、其下游基因 VEGF 的mRNA和蛋白的表达增加。TSA可抑制HIF-1α的蛋白表达，进而抑制其下游基因VEGF的表达，从而发挥抗肿瘤血管生成的作用，并且呈量效和时效关系。

关键词:  , 低氧；血管生成；缺氧诱导因子-1&alpha, ；血管内皮生长因子；曲古抑菌素A

Abstract: Objective: The current study was designed to explore whether the inhibitory effect of histone deacetylase inhibitor trichostatin A (TSA) are associated with the expressions of hypoxia-induced HIF-1α and VEGF  of tongue squamous cell carcinoma SCC-6 cell line in vitro.  Methods: SCC-6 cells were treated with desferrioxamine (DFX) and trichostatin A (TSA) in different concentrations at various time periods in vitro. Expressions of HIF-1α and VEGF were detected by real-time reverse transcription PCR and Western Blot on mRNA and protein levels respectively. The data were analyzed by Student's t test and one-way analysis of variance. Statistical analyses were performed by SPSS 14.0 software. Results: ①The expression of HIF-1α protein, VEGF mRNA and protein increased when treated with hypoxia simulacrum DFX. ②TSA significantly inhibited the expressions of HIF-1α proteins, VEGF mRNA and protein (P<0.05) in vitro in a time- and dose-dependent manner. ③The transcription activity of HIF-1α occurred at the protein level.  Conclusion: Hypoxia can induce the expression of  HIF-1α and its target gene VEGF in vitro， which can be inhibited by histone deacetylase inhibitor TSA in a dose- and time-dependent manner.

Key words: hypoxia, angiogenesis, hypoxia-inducible factor 1-α(HIF-1α), vascular endothelial growth factor (VEGF), trichostatin A(TSA)

中图分类号: 

• R739.86