The Inhibitive Effect Of COX-2 Inhibitor NS398 On Cancer Growth Of Salivary Adenoid Cystic Carcinoma SACC-83 Cells

PrefaceAdenoid cystic carcinoma(ACC) is one of the most common malignant tumor of salivary gland origin,representing 10%to 15%of salivary gland malignancies.In the maxillofacial region,the salivary glands are particularly affected by ACC and,less frequently,the lacrimal glands.The characteristic clinicopathologic features of this tumor are perineural spread,local recurrences,and distant metastases.ACC tends to spread along nerves(perineural invasion) or through the bloodstream.It only spreads to the lymph nodes in about 5%to 10%of cases.Tumor growth for ACC is often slow, and patients may live a long time with metastatic disease。Cyclooxygenase is an important rate-limiting enzyme of the process for prostaglandin biosynthesis,which has two forms,namely COX-1 and COX-2.Two COX isoforms with distinct tissue distributions and physiological functions have been identified.Cyclooxygenase-1(COX-1) is constitutively expressed in many tissues and plays important roles in the control of homeostasis.Conversely,COX-2 is an inducible enzyme and is activated by extracellular stimuli such as growth factors and pro-inflammatory cytokines.Recent investigations indicated that over-expression of COX-2 is frequently found in many types of cancer including colon,lung,breast, pancreas and head and neck cancers and is usually associated with poor prognosis and short survival.The contribution of COX-2 to tumorigenesis has been intensively studied.Several mechanisms are considered to mediate the tumorigenic activity of COX-2.First,PGE2, and the main metabolite of COX-2,is a growth promoter and may directly stimulate proliferation of cancer cells.Second,COX-2 is an angiogenic stimulator and may increase the production of angiogenic factors and migration of endothelial cells.Third, COX-2-derived PGE2 is an anti-apoptotic molecule which may prevent apoptosis induced by anti-cancer drugs.Fourth,PGE2 is an immuno -regulatory molecule which may suppress the anti-tumor activity of natural killer cells and macrophages.Fifth, COX-2 expression may increase the invasive ability of tumor cells and is closely linked with lymph node metastasis.COX-2 not only plays an important role in inflammation,but also has relation with the occurrence,development and metastasis of various tumors.Research has shown that,in OSCC,especially in the early stage of tumors,COX-2 show over-expression.In vitro study of some tumor cells,such as ovarian carcinoma, esophageal carcinoma,prostatic carcinoma,hepatoma,gastric carcinoma,colon carcinoma,et al.specific inhibitor of COX-2,NS398 can inhibit the proliferation of tumor cells,promoting the apoptosis of tumor cells.We treat salivary adenoid cystic carcinoma cell line with specific inhibitors of cyclooxygenase-NS398,and the goal of this experiment is to study NS398 on the impact of proliferation and apoptosis of SACC cells,to explore the relationship between COX-2 and salivary adenoid cystic carcinoma.It also provides a theoretical basis for further research about the pathogenesis in salivary adenoid cystic carcinoma and provides a new way of thinking for the salivary adenoid cystic carcinoma of the targeted therapy.Material and MethodsSACC-83 cell lines bestowed by school of stomatology in Beijing University. NS398(sigma);MTT(sigma);DMSO(sigma).SACC-83 cells cultured in vitro were treated with NS398,inverted phase contrast microscope and transmission electron microscope were used to observe the cell morphological changes.MTT assay was used to study the inhibitive effect of NS398 on the growth of SACC-83 cells,and investigate the time-effect relationship and dose-effect relationship between NS398 and SACC-83 cells.The statistical date was analyzed by SPSS13.0 software.Student's t test and repeated-measure ANOVA were used to analyze the date. ResultSACC-83 cells treated with NS398 showed cytoplasmic vacuolization,apoptotic bodies,and microvilli on the cell surface disappeared.The SACC-83 cell culture median contained 0,50,100,150,200μmol/L NS398,and individually cultured for 24,48,72,96 hours.The inhibitive effect increased with the time prolonging and the concentration increasing.The effect was most obvious with 150μmol/L NS398 cultured for 72 hours(concentration:P＜0.05,time:P＜0.05).ConclusionNS398 can inhibit the growth of SACC-83 cells.The inhibitive effect NS398 on SACC-83 cells is dose-dependent and time-dependent.NS398 may play an important role in the treatment of salivary adenoid cystic carcinoma.