Departments of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
J Environ Pathol Toxicol Oncol. 2012;31(4):349-56. doi: 10.1615/jenvironpatholtoxicoloncol.2013005365.
Cigarette smoke has been documented to be related to the development of cancer. However, the exact mechanism for the carcinogenic action of cigarette smoke is still unknown. Nicotine is recognized to be the major compound in cigarette smoke and has been suggested to play a role in oral cancer via a cyclooxygenase (COX)/ prostaglandin-dependent pathway. This study was designed to evaluate the action of nicotine in the oral cancer cell and to further examine whether COX-2 is responsible for expression of tumor-associated angiogenic vascular endothelial growth factor (VEGF) in vitro. Viability of human oral squamous cancer cells (BHY) was measured using MTT assay. Protein expression was determined by Western blot and immunoassay kits. We found that exposure of BHY cells to nicotine (200 µg/mL for 6 hours) resulted in 2.9-fold induction of COX-2 expression as well as a 4-fold increase in VEGF levels compared with a control group. Pretreatment with celecoxib inhibited nicotine-induced change in the expression of VEGF and COX-2. The results suggest that stimulation of COX-2 and VEGF expression can contribute as important factors in the tumorigenic action of nicotine in oral cancer progression. This effect can be blocked by celecoxib, suggesting an interaction of nicotine and COX-2 pathways.
香烟烟雾已被证实与癌症的发生有关。然而，香烟烟雾致癌的确切机制仍不清楚。尼古丁被认为是香烟烟雾中的主要化合物，并被认为通过环氧化酶（COX）/前列腺素依赖途径在口腔癌中发挥作用。本研究旨在评估尼古丁在口腔癌细胞中的作用，并进一步研究 COX-2 是否负责体外肿瘤相关血管生成血管内皮生长因子（VEGF）的表达。通过 MTT 测定法测量人口腔鳞状癌细胞（BHY）的活力。通过 Western blot 和免疫试剂盒测定蛋白表达。我们发现，与对照组相比，BHY 细胞暴露于尼古丁（200μg/ml 6 小时）导致 COX-2 表达增加 2.9 倍，VEGF 水平增加 4 倍。预先用塞来昔布处理可抑制尼古丁诱导的 VEGF 和 COX-2 表达的变化。结果表明，COX-2 和 VEGF 表达的刺激可作为尼古丁在口腔癌进展中的致癌作用的重要因素。这种作用可以被塞来昔布阻断，表明尼古丁和 COX-2 途径之间存在相互作用。
