Santhi W S, Sebastian Paul, Varghese Bipin T, Prakash Om, Pillai M Radhakrishna
Department of Molecular Medicine, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
Exp Mol Pathol. 2006 Oct;81(2):123-30. doi: 10.1016/j.yexmp.2006.05.001. Epub 2006 Jul 5.
Oral cancer is a major health problem in many parts of the world including India. The molecular mechanisms involved in oral tumorigenesis are not completely understood. Although surgery continues to be the most common treatment modality for this cancer, survival rates of oral cancer patients have still not significantly improved over the last few decades. Classical diagnostic methods are still not sensitive enough in detecting completeness of surgery and assessing minimal residual disease. This study investigated the role of NF-kappaB and COX-2 both in oral cancer progression and assessment of minimal residual disease. Expression of NF-kappaB proteins and its inhibitory protein IkappaB-alpha was evaluated using immunohistochemistry, ELISA and EMSA, while RT-PCR was used to detect COX-2 expression. Cytoplasmic expression as well as nuclear translocation of NF-kappaB proteins increased with histological progression of oral cancer (from normal to leukoplakia to cancer). A similar pattern of expression was observed for COX-2 also. NF-kappaB proteins, both cytoplasmic and nuclear, had a significant negative correlation from tumor to surgical margin to extra margin; COX-2 paralleled the expression of NF-kappaB proteins. Our results thus point to NF-kappaB and COX-2 as participants in oral tumor progression and also to the validation of these two molecular markers in assessing minimal residual disease.
口腔癌是包括印度在内的世界许多地区的一个主要健康问题。口腔肿瘤发生所涉及的分子机制尚未完全明确。尽管手术仍然是这种癌症最常见的治疗方式,但在过去几十年里,口腔癌患者的生存率仍未显著提高。传统的诊断方法在检测手术完整性和评估微小残留病灶方面仍然不够敏感。本研究调查了NF-κB和COX-2在口腔癌进展以及微小残留病灶评估中的作用。使用免疫组织化学、酶联免疫吸附测定(ELISA)和电泳迁移率变动分析(EMSA)评估NF-κB蛋白及其抑制蛋白IκB-α的表达,而逆转录聚合酶链反应(RT-PCR)用于检测COX-2的表达。随着口腔癌组织学进展(从正常到白斑再到癌症),NF-κB蛋白的细胞质表达以及核转位增加。COX-2也观察到类似的表达模式。从肿瘤到手术切缘再到切缘外,细胞质和细胞核中的NF-κB蛋白均呈显著负相关;COX-2与NF-κB蛋白的表达平行。因此,我们的结果表明NF-κB和COX-2参与口腔肿瘤进展,并且这两种分子标志物在评估微小残留病灶方面具有有效性。