School of Dentistry, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681 Partenon, 90619-900 Porto Alegre, Brazil.
Invest New Drugs. 2012 Aug;30(4):1371-8. doi: 10.1007/s10637-011-9701-x. Epub 2011 Jun 14.
This study evaluated the relevance of CXCR2 chemokine receptors in oral squamous cell carcinoma, by means of in vitro and in vivo approaches. The in vitro incubation of the selective and non-peptide CXCR2 receptor antagonist N-(2-hydroxy-4-nitrophenyl)-N9-(2-bromophenyl) Urea (SB225002; 25 to 800 nM) produced a time- and concentration-dependent inhibition of SCC158 (rat) and HN30 (human) cell lines viability. Conversely, this antagonist did not significantly affect the viability of the immortalized keratinocyte lineage, HaCaT. Additionally, the incubation of human IL-8 and rat CINC-1 CXCR2 agonists produced a concentration-related increase on HN30 and SCC158 proliferation. The submucosal injection of SCC158 cells (5 × 10(6) cells) into the tongue of Fischer 344 rats induced tumor development, which displayed typical clinical features. Immunohistochemical analysis of rat tongue biopsies revealed a marked increase of CXCR2 receptor immunoreactivity, which was accompanied by augumented expression of VEGF and caspase-3. Our data suggests an important role for CXCR2 receptors in oral squamous cell carcinoma.
本研究通过体外和体内方法评估了 CXCR2 趋化因子受体在口腔鳞状细胞癌中的相关性。选择性非肽 CXCR2 受体拮抗剂 N-(2-羟基-4-硝基苯基)-N9-(2-溴苯基)脲 (SB225002；25 至 800 nM) 的体外孵育产生了时间和浓度依赖性的 SCC158(大鼠)和 HN30(人)细胞系活力抑制。相反，该拮抗剂对永生化角质形成细胞系 HaCaT 的活力没有显著影响。此外，人 IL-8 和大鼠 CINC-1 CXCR2 激动剂的孵育导致 HN30 和 SCC158 增殖呈浓度相关增加。将 SCC158 细胞(5×10(6)个细胞)注入 Fischer 344 大鼠舌的黏膜下诱导肿瘤发展，显示出典型的临床特征。对大鼠舌活检的免疫组织化学分析显示 CXCR2 受体免疫反应性明显增加，同时 VEGF 和 caspase-3 的表达增加。我们的数据表明 CXCR2 受体在口腔鳞状细胞癌中具有重要作用。
