Mohamed Khaled M, Le Anh, Duong Hai, Wu Yidi, Zhang Qunzhou, Messadi Diana V
Faculty of Dentistry, Suez Canal University, Suez Canal, Egypt.
Exp Mol Pathol. 2004 Apr;76(2):143-52. doi: 10.1016/j.yexmp.2003.10.005.
Understanding the development and progression of oral cancer is critical in the quest for successful therapeutic intervention. The hypoxic microenvironment present in human oral tumor in vivo may actively influence tumor growth and neovascularization. This study correlates expression of both VEGF and HIF-1alpha in normal keratinocytes and oral cancer cell lines and determine whether hypoxia played a role in VEGF and HIF-1alpha regulation. Three human oral cancer cell lines and three normal keratinocytes were exposed to both normoxia and hypoxia culture conditions. Northern and Western blot analysis were used to assess VEGF and HIF-1alpha expression in the different culture conditions. ELISA assays were performed to measure VEGF production in the different cell lines tested. Hypoxia upregulated VEGF and HIF-1alpha expression on both normal and oral cancer cell lines, with a statistically significant difference between normal and oral cancer cell lines. Pattern of hypoxia-induced VEGF mRNA level tightly followed the HIF-1alpha mRNA expression in the cell lines tested. These results suggest that hypoxia regulates both VEGF and HIF-1alpha expression in head and neck carcinoma cell lines, thus establishing a biochemical pathway between tumor hypoxia and neoangiogenesis in these aggressive neoplasms.
了解口腔癌的发生和发展对于寻求成功的治疗干预至关重要。人类口腔肿瘤体内存在的缺氧微环境可能会积极影响肿瘤生长和新血管形成。本研究关联了正常角质形成细胞和口腔癌细胞系中VEGF和HIF-1α的表达，并确定缺氧是否在VEGF和HIF-1α调节中发挥作用。三种人类口腔癌细胞系和三种正常角质形成细胞分别暴露于常氧和缺氧培养条件下。采用Northern和Western印迹分析评估不同培养条件下VEGF和HIF-1α的表达。进行ELISA测定以测量所测试的不同细胞系中VEGF的产生。缺氧上调了正常和口腔癌细胞系中VEGF和HIF-1α的表达，正常细胞系和口腔癌细胞系之间存在统计学上的显著差异。在测试的细胞系中，缺氧诱导的VEGF mRNA水平模式与HIF-1α mRNA表达紧密相关。这些结果表明，缺氧调节头颈部癌细胞系中VEGF和HIF-1α的表达，从而在这些侵袭性肿瘤中的肿瘤缺氧和新血管形成之间建立了一条生化途径。
