Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul 110-749, Korea.
Mol Cells. 2010 Feb 28;29(2):185-94. doi: 10.1007/s10059-010-0026-y.
Although many studies highlighted cyclooxygenase2 (COX2) inhibition as a promising therapeutic strategy for cancer, more evidence is needed for clinical application. The purpose of this study was to investigate the feasibility of COX2 inhibition as a strategic treatment modality for head and neck carcinoma (HNC). We tested COX2 inhibitor, celecoxib in six types of HNC cells and analyzed the expression changes in proteins related to angiogenesis and apoptosis in vitro. We also evaluated proliferation, gelatinolysis and in vitro invasion. We used a hamster carcinogenesis model and a mouse tumorigenesis model for the in vivo evaluation of COX2 inhibition. We performed immunohistochemistry to assess changes in the expression of COX2, survivin and angiogenesis. Celecoxib administration caused decreases in the expressions of COX2, VEGF and survivin in vitro. Proliferation, in vitro invasion and gelatinolytic activity were reduced in HNC cell lines, but the effect was inconsistent across lines. COX2 inhibition retarded oral carcinogenesis from an early carcinogenic stage with increased apoptosis and decreased survivin expression. COX2 inhibition did not inhibit tumor growth, even with the COX2 downregulation and decrease in neovascularization. We conclude that COX2 inhibition has a chemopreventive effect, but its application as a treatment of HNC in a clinical setting still requires further research to overcome its limited anti-cancer effects.
尽管许多研究强调环氧化酶 2（COX2）抑制是癌症治疗的一种很有前途的策略，但仍需要更多的临床应用证据。本研究旨在探讨 COX2 抑制作为头颈部癌（HNC）的一种治疗策略的可行性。我们在六种 HNC 细胞中测试了 COX2 抑制剂塞来昔布，并分析了体外与血管生成和细胞凋亡相关的蛋白表达变化。我们还评估了增殖、明胶酶解和体外侵袭。我们使用仓鼠致癌模型和小鼠肿瘤发生模型进行 COX2 抑制的体内评估。我们通过免疫组织化学评估 COX2、生存素和血管生成表达的变化。塞来昔布给药导致体外 COX2、VEGF 和生存素的表达减少。HNC 细胞系的增殖、体外侵袭和明胶酶解活性降低，但在不同细胞系之间效果不一致。COX2 抑制可延缓口腔癌从早期致癌阶段发展，促进细胞凋亡和降低生存素表达。COX2 抑制并不能抑制肿瘤生长，即使 COX2 下调和新生血管减少。我们得出结论，COX2 抑制具有化学预防作用，但将其作为 HNC 的治疗方法在临床应用中仍需要进一步研究以克服其抗癌作用有限的问题。
