Studies on the involvement of inflammatory stimuli and immortalization of cells in tongue carcinogenesis and cancer chemoprevention

我们前期的研究表明，考克斯-2蛋白的表达参与了4-NQO诱导的大鼠舌癌的发生。本研究采用考克斯-2（COX-2）特异性抑制剂尼美舒利（nimesulide）对4-NQO诱导的大鼠舌癌发生的影响。用4-NQO（20 ppm饮水）连续8周诱发大鼠舌鳞状细胞癌。在启动期（10周）或促进期（22周），他们还以0.01%或0.04%的剂量喂食混合有尼美舒利的饮食。实验在开始后32周终止。研究结束时，舌鳞癌的发生率为48%在4-NQO单独给药组中（13/27只大鼠），20% 4-NQO+0.01%尼美舒利组（3/15只），13%（13/15只）4-NQO+0.04%尼美舒利组为2/15，4-NQO→0.01%尼美舒利组为42%（5/12），4-NQO →0.04%尼美舒利组为8%（1/12）。因此，无论是在舌癌发生的起始阶段还是促进阶段，均能显著抑制舌癌的发生（P<0.05）。尼美舒利单独给药组（0.04%）和未给药对照组大鼠均未出现舌质 *。提示考克斯-2特异性抑制剂尼美舒利可用于舌癌化学预防的临床研究。众所周知，饮用水中的4-NQO处理特异性地诱发舌肿瘤。然而，在本研究中，4-NQO暴露诱发上颌骨的腭和GI的鳞状细胞癌以及舌癌。喂饲尼美舒利也能抑制th* 肿瘤的发展。

Our previous study indicated that expression of COX-2 protein involves in 4-NQO-induced rat tongue carcinogenesis. In this year, therefore, we investigated possible modifying effect of nimesulide, which specific inhibitor of COX-2, on 4-NQO-induced rat tongue tumorigenesis.A total of 97 male F344 rats aged 4 weeks were used. Rats were given 4-NQO (20 ppm in drinking water) for 8 weeks to induced tongue squamous cell carcinoma. They were also fed the diets mixed w* nimesulide at a dose of 0.01% or 0.04% during the initiation (10 weeks) or promotion phase (22 weeks). The experiment was terminated 32 weeks after the start. At the end of the study, the incide* of tongue squamous cell carcinoma were 48% (13/27 rats) in the 4-NQO alone group, 20% (3/15 rats) in 4-NQO+0.01% nimesulide group, 13% (2/15 rats) in the 4-NQO+0.04% nimesulide group, 42% (5/12 rats) in the 4-NQO→0.01% nimesulide group, and 8% (1/12 rats) in the 4-NQO→0.04% nimesulide group. Thus, feeding of nemesulide during either the initiation or promotion pahse *tumorirgenesis significantly inhibited the development of tongue carcinoma (P<0.05). No tongue tum* were present in rats of nimesulide alone (0.04%) and untreated control. These results suggest that a COX-2 sepcific inhibitor nimesulide is applicable for human clinical trial for chemoprevention of tongue cancer. The studies on mechanisms of inhibition are ongoing in our laboratory.It is well known that the treatment of 4-NQO in drinking water specifically prodeces tongue neoplas* However, in the present study, 4-NQO exposure induced squamous cell carcinoma in the palate and gi*of the maxilla as well as tongue carcinoma. Feeding of nimesulide also inhibited the development of th*tumors.