Experimental Study Of Influence Of Celecoxib In Tumor Growth Of Human Medullary Thyroid Cancer In Nude Mice

Objective To observe the depressant effect of Celecoxib in transplant tumor growthof medullary thyroid carcinoma in nude mice.Background Though medullary thyroid carcinoma is rare, because of the highmalignancy, rapid progression and poor prognosis, many patients have lost theopportunity of radical operation when they seek for medical treatments, andmedullary thyroid carcinoma is not sensitive to radiotherapy, chemotherapy and131Itreatment,there is lack of satisfactory treatment, so the research of new anti medullarythyroid cancer drug is importantly significance. At present,the different COX-2selective inhibitors’ effects on tumor cells become hot issues in clinical research, butstudies of effects on thyroid cancer are few, especially because of the thyroid cancercells culturing is difficult, as well as establishing tumor animal model, studies on themedullary thyroid cancer have not been done yet.Methods40mice were randomly divided into4groups marked A,B,C and D：Control group、Celecoxib group、Doxorubicin group and Celecoxib joint Doxorubicingroup. All vaccination animal models were established by being injected of2×106ofhuman medullary thyroid carcinoma TT cells subcutaneously. The celecoxib dose is300mg/kg per day, and doxorubicin dose is2mg/kg per day. Medicines were given for1week after0.5cm tumor nodus appeared in the injection region, tumor volumes andweight of mice were measured. After3weeks tumor inhibition was calculated.Theexpression level of Cyclooxegenase-2（COX-2）, Matrix Metalloproteinases-9（MMP-9）, Vascular endothelial growth factor（VEGF）of the vaccination tumor、liver、lung and renel tissues were detected by immunohistochemistry.The expressionlevel of Cyclooxegenase-2（COX-2）, Matrix Metalloproteinases-9（MMP-9）,Vascular endothelial growth factor（VEGF）of the vaccination tumor tissues weremeasured by RT-PCR and Western blot。Results The inhibition rates in A,B,C,D were0%,45.37％、49.71％、69.68％ respectively，and B,C,D group showed more effective in suppressing the tumorgrowth than the control group(P<0.05), no obviously difference was found in eachgroups. The tumor volume and weight of each treatment group was significantly lessthan that of the control group(P<0.05),there is no significant difference between thetreatment group (P>0.05), there was significant difference at the tumor weightbetween B group, C group and D group (P<0.05). The protein expression of COX-2,MMP-9,VEGF and COX-2, MMP-9,VEGF mRNA in A group were obviouslyhigher than that of B、C and D group (P<0.05), all of them in B、C group wereobviously higher than that of D group (P<0.05),but were no difference in B,C groupthemselves (P>0.05). In each group, tumor cells invade in all of hepatic tissues, andCOX-2、MMP-9、VEGF were positively correlated to hepatic tissues.Conclusion1、The nude mice model transplanted with human medullary thyroid carcinomawas successfully established, which has similar morphological character with humanmedullary thyroid carcinoma, provided an ideal animal model for studying medullarythyroid carcinoma;2、Celecoxib can inhibit synthesis of protein expression of COX-2、MMP-9andVEGF,decrease prostaglandins production and inhibit thyroid tumor angiogenesis byinhibit prostanoid-like COX-2production;3、Celecoxib can inhibit the growth of vaccination tumors of medullary thyroidcarcinoma, promote cell apoptosis, to prevent tumorigenesis or inhibition tumorgrowth, so it has anti-tumor effect, which could be strengthen when combined withDoxorubicin.