Expression Of The COX-2 And INOS In Laryngeal Squamous Cell Carcinoma And Their Clinical Significance

Laryngeal carcinoma is one of the most common malignant neoplasm in head and neck.The incidence is upgrade year by year. There are many traditional methods such as surgery operation, radiotherapy, chemotherapy.They saved many lives who were suffered from tumour ,but in some of advanced stage,recurrence and metastasis of laryngeal carcinoma,the curative effect is poor. As the human genome project is completed and some breakthrough of the tumour foundation sphere,The gene treatment of tumor displays good foreground.To find the valid target gene is important of the therapy with tumour.COX-2 is also named prostaglandins superoxide synthetase.one of the key enzymes in the conversion of arachidonic acid to prostaglandins. It has exists in two distinct isoforms, a constitutive enzyme (COX-1) and an inducible form (COX-2).Growth factors, tumor promoters,cytokines, oncogenes, and other inflammatory mediators have been found to induce COX-2 expression.Recently, the importance of COX-2 in carcinogenesis has been recognized suggesting that it may be a promising chemotherapic target.COX-2 has been found in many tumours such as esophageal carcinoma, nasopharyngeal carcinoma, colon carcinoma, Hepatoma, thyroid carcinoma, gastric carcinoma,et al.Currently study enunciates that there are some mechanisms of COX-2 in the process of tumours.1.cox-2 can promote cell proliferation and inhibit apoptosis of tumous;2. cox-2 can promote the tumour's invasion and metastasis ; 3. cox-2 can promote tumour's angiogenesis, increase the MVD of tumours;4. cox-2 can inhibit immunity reaction of organism,promote precarcinogen to carcinogen.Nitric oxide synthases (NOS) is the key enzyme in the conversion of nitric oxide.There are three isoforms of NOS: inducible(iNOS), endothelial (eNOS), and neural (nNOS). Generally, nNOS and eNOS are expressed constitutively in neurons and endothelial cells.Inducible NOS is expressed in macrophages,tumour cells,neutrophils, endothelial cells, hepatocytes,and many other cell types. It is induced most importantly by cytokines and can generate locally high concentrations of NO for prolonged periods.And participate in the pathophysiological process of tumours.iNOS has been found in many tumours such as intestine carcinoma, pancreatic carcinoma,hepatoma,cancer of the cervix,gastric carcinoma ,etc.There are some mechanisms of iNOS in the process of tumours.1. iNOS can promote tumours angiogenesis, distend the blood vessel of tumours;2. iNOS can induce generating of NO and NO can induced the damage of DNA;3. In some definite condition,iNOS can induced apoptosis of tumous;The role of NO in tumour-cell apoptosis and survival depends on the cell type, the concentration of NO in the cellular microenvironment, the time of cellular exposure to NO, and possibe other factors.When the concentration of NO is high,it can antitumour, when the concentration of NO is low,it can promote the progression and metastasis of tumours.In recent years, research displays that reactive oxygen species (ROS) and reactive nitrogen species (RNS) can function both as initiators and promoters in carcinogenesis. iNOS and COX-2 are significant enzyme mediate the generation of ROS and RNS. iNOS and COX-2 are expressed respective in some tumours,in the same time,they interreaction in the progress of tumours.They resemble in some cases such as tissue distribution, express and regulation.They are cooperated express in the proceed of some pathophysiological.It has a cross talk between them.Nowadays,some selective inhibitor of COX-2 such as cleecoxib was apply in the FAP. Some study shows that combine the inhibitor of COX-2 and iNOS have better effect than only one of them apply in therapia tumours.There was seldom of it in the research of laryngeal carcinoma.To study the expression of cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS)in laryngeal squamous cell carcinoma(LSCC) ,and their relationship with tumor clinical pathology characteristics.We used the method of immunohistochemical staining(S-P method). And we detected COX-2 and iNOS protein which were performed in 52 cases of LSCC by SP.20 cases squamous epidermis near cancer and 16 cases normal laryngeal mucosa.The relationgship between the expression of COX-2,iNOS with the clinical pathology characteristics were analysed. And the results display as following : 1. The expression rates of COX-2 protein were respectively 79%,20%,0% in LSCC,squamous epidermis near cancer,normal laryngeal mucosa. The expression of COX-2 in LSCC was up-regulated which had significant difference(P<0.01)from that of both squamous epidermis near cancer and normal laryngeal mucosa. There is no difference between the group of squamous epidermis near cancer and the group of normal laryngeal mucosa. There was not significant correlation between the expression of COX-2 with the age,gender of patient, the site of its growth and lymph node transfer. However there was a significant correlation between the expression of COX-2 with the tumor TNM stage(P < 0.01)and the type of pathology(P<0.05).2. The expression rates of iNOS protein were respectively 67%,25%,0% in LSCC,squamous epidermis near cancer,normal laryngeal mucosa. The expression of iNOS in LSCC was up-regulated which had significant difference(P<0.01)from that of both squamous epidermis near cancer and normal laryngeal mucosa. There is no difference between the group of squamous epidermis near cancer and the group of normal laryngeal mucosa.There was not significant correlation between the expression of iNOS with the age,gender of patient and the site of its growth .However there was a significant correlation between the expression of COX-2 with the tumor TNM stage(P<0.05);the type of pathology(P<0.01)and the lymph node transfer(P<0.05).3. The expression of COX-2 and iNOS in LSCC had significantly positive correlation(P<0.01). We can get the conclusion as following, COX-2 and iNOS both promote the process of genesis or progress of LSCC. They also have a cooperation in the genesis and progress of LSCC. The expression of iNOS in LSCC is up-regulated which has relationship with the lymph node transfer. There may be two new treatment targets.They afford some theory that can use inhibitor in the treatment of LSCC.In conclusion,we examined the expression of COX-2 and iNOS together in laryngeal carcinoma tissues,adjacent tissues of laryngeal carcinoma,normal tissues of laryngeal.The result indicated that laryngeal carcinoma tissues was sensitive to the examination of COX-2 and iNOS. COX-2 and iNOS are all correlate with laryngeal carcinoma biology behavior.They are cooperated expressing in the laryngeal carcinoma and afford some theory that can use gene therapy in the treatment of LSCC.