Expression Of COX-2,MMP-9,VEGF And RET In Thyroid Cancer And Study Of Celecoxib On Tumor Cell Growth

Cyclooxygenase is the only rate-limiting enzyme of prostaglandin(PG). By far two subtypes were found. There are COX-1 and COX-2. COX-1 expression is stable in normal cells.COX-2 can induce PG in pathological state.In recent years some studies found that COX-2 plays an important role in the cancinogenesis, development and prognosis by inducing angiogenesis and cell growth and inhibiting cell apoptosis. It is reported that COX-2 expression was found in gastric cancer,liver cancer and pancreatic cancer,et al.However,the mechanism is unclear.Based on this, some scientists investigated that COX-2 inhibitors have anti-tumor effect by some research about colon cancer,pancreatic cancer and liver cancer in vitro and in vivo.With the low activity of MMP,cancer cell invasion decrease. By far the research on COX-2 and its specific inhibitor in thyroid cancer is few.Lymph node metastasis rate of thyroid papillary carcinoma(PTC) is 83.3%.Eevn there is no lymph node metastasis(N0),secret metastasis is 46%~72%. As far there is no reliable examination method. Thyroid medullary cancer and undifferentiated cancer is treatment focus. Many patients missed the operation,and cells is unsensitive to chemotherapy and radiotherapy. This study is to investigate the relationship of COX-2,MMP-9,VEGF and RET with cancerogenesis and metastasis. From these proteins we want to find the effective markers to diagnosis the early thyroid cancer and metastasis to treat it correctly.Meantime, we examine the COX-2 selective inhibitor-celecoxibi on cell growth to supply a new method for thyroid biological treatment.Expression of COX-2,MMP-9,VEGF and RET on thyroid papillary cancer and its clinical significanceIn this study COX-2,MMP-9,VEGF and Ret expression in thyroid cancer is high than that of thyroid benigh tumors by immunohistochemistry and RT-PCR. The difference is significant statistically(P<0.05). COX-2 and MMP-9 are the most sensitive markers. And COX-2 and MMP-9 expressions is related to age,membrane integrality,tumor size and clinical stage. The difference is significant statistically(P<0.05). COX-2 expression is related to lymphatic metastasis(P<0.05),unrelated to sex(P>0.05);COX-2 expression is related to MMP-9,VEGF and Ret expression(sP<0.05).Through several genes filtration,MMP-9 is regarded as a sensitive marker of thyroid early diagnosis ,and sensitivity rate is 90.9% and specific rate is 90.0%.COX-2 expression can work as a marker to evaluate lymph node metastasis,and sensitivity rate is 77.8% and specific rate is 66.7%.Therefor,Fine needle aspiration combined with COX-2 and MMP-9 can be helpful to early diagnosis and evaluate lymph node metastasis to choose reliable treatment method. PTC patient with lymph node metastasis can get effective treatment,meantime those patient without lymph node metastasis avoid inevitable operationStudy of Celecoxib on human thyroid medullary cancer TT cell line growth In this study by 3H-TdR mixtration method human thyroid medullary cancer TT cell line growth was observed with different concentration Celecoxib on different time point. The results are that Celecoxib can inhibit cell proliferation which show positive correlation with concentration and time. By FCM TT cell line DNA synthesize proliferation cycle was observed. Celecoxib can make tumor cell stop at G0/G1 phase.After 48h with celecoxib action COX-2 mRNA,MMP-9 mRNA and VEGF mRNA expressions decreased by 26.1%,28.8% and 34.2% by RT-PCR,and three proteins have correlation. This further comfirm that celecoxib can inhibit angiogenesis by reducing VEGF and MMP-9 expressions. Meantime, celecoxib can make Survivn mRNA decrease by 30.6% and Caspase increase by 19.8% . This shows celecoxib can inhibit cell growth by inducing cell apoptosis.Conclusion:Fine needle asiparation combined with COX-2 and MMP-9 expression in thyroid neoplasms can act as an early diagnosis method for thyroid cancer and evaluate lymph node metastasis, and it can direct operation type. COX-2 specific inhibitors celecoxib can inhibit cell growth and development by inhibiting angiogenesis ,inducing cell apoptosis and promoting cell cycle blockade. These proteins can possibly work as new targets for drug treatment of thyroid cancer.