The Expression Of Cyclooxygenase-2 In Uterine Cervix Cancer And Precancerous Change

Uterine cervix cancer is the most frequent gynecologymalignant tumor. In recent ten years, the onsets of uterine cervixcancer show a young tendency. Because of the longer precancerouschange phase, it is absolutely important to make early diagnosis,precaution and early treatment. Cyclooxygenase-2(COX-2)which isthe key rate-limiting enzyme in prostaglandin synthesis processexpresses in many tumor tissue and cell, but until now, there is fewreports about the significant of COX-2 in uterine cervix cancer andprecancerous change. In this study, we investigated the relationshipof COX-2 with uterine cervix cancer and precancerous change usingimmunohistochemical method , Western blotting and RT-PCR.COX-2 protein and mRNA express was quantitative studied and itsrole was approached at different levels in uterine cervix cancer.Meanwhile, we detected the protein expression of matrixmetalloproteinase-9(MMP-9), cysteine proteinase(caspase-3)andvascular endothelial growth factor(VEGF)in uterine cervix cancertissue using immunohistochemical method, so we can study therelation of COX-2 with them and approach the role of COX-2 inuterine cervix cancer further. Our object is to provide theory basis inthe manufacture of COX-2 selective inhibitor.Firstly, we detected the expression of COX-2 in uterine cervixcancer and precancerous change using immunohistochemical method.The results show that there is no expression in normal cervix, 19%of COX-2 positive rate in chronic cervicitis, 2 of 9 positive case incervical intraepithelial neoplasiaI (CIN I), no expression in 9 CIN IIcases, 37.5% of COX-2 positive rate in CIN III cases, 23.5% ofCOX-2 positive rate in the whole CIN group, 84.8% of COX-2positive rate in uterine cervix cancer. The differences of COX-2expression between normal cervix and chronic cervicitis, CIN,uterine cervix cancer are all significant(P<0.05), furthermore,COX-2 positive rate was gradually increased in chroniccervicitis→CIN→ uterine cervix cancer, which is according with thedeveloping process of cervicitis→CIN→ uterine cervix cancer. Theresults indicate that COX-2 has a close correlation with uterinecervix cancer and it may be the early indicate of uterine cervixcarcinogenesis. The results provide theory basis in the manufactureof COX-2 selective inhibitor.Secondly, we detected COX-2 protein expression usingWestern blotting and analyzed the relationship between COX-2proteins with clinical patho-factors of uterine cervix cancer. Theresults show that COX-2 expression amount was gradually increasedin uterine cervix cancer I stage , II stage and III stage(Thedifferences are all significant P<0.05), it has no differences amongdifferent pathology types, and the expressions are higher in lymphglands metabasis group( P<0.05).Going step further, in order to investigate the relationshipbetween COX-2 genes with clinical patho-factors of uterine cervixcancer, we detected COX-2 gene expression using RT-PCR. Theresults show that COX-2 mRNA has no significant differencesamong different clinical stage and different pathology types, and theexpressions are higher in lymph glands metabasis group( P<0.05),which is coincident with Western blotting results. These resultsindicate that COX-2 takes part in the development of uterine cervixcancer and it is gradually increased following the advancement andmetabasis of uterine cervix cancer, which may be help to judge theprognosis of uterine cervix cancer.Meanwhile, we detected the protein expression of MMP-9,caspase-3 and VEGF in uterine cervix cancer tissue usingimmunohistochemical method and we analyzed the dependablity ofCOX-2 with them. The results indicate that COX-2 has positivecorrelation with MMP-9(r=0.801,p<0.05)and caspase-3, and hasindependence with VEGF(r=0.145,p>0.05).At present, COX-2 is considered to take part in the formation ofcarcinoma by inhibiting cell apoptosis and immunologic function,promoting Angiogenesis, increasing invasion ability of tumour cells,and promoting the transform from precancerous change to cancer.Our results indicate that COX-2 has positive correlation withMMP-9 and caspase-3, which illustrates COX-2 takes part in theformation of uterine cervix cancer by increasing invasion ability oftumour cells and inhibiting cell apoptosis. COX-2 has nodependence with VEGF probably due to the shortage of sample orsampling error. It also may be that COX-2 and VEGF are twoindependent factors, or they play a part in uterine cervix cancer indifferent phase. Of course, other complex factors should beconsidered.Some researches indicate that COX-2 is the independent factorof uterine cervix cancer prognosis and can be one of index of uterinecervix cancer prognosis. Gaffney et al [13] make a study about thesurvival of uterine cervix cancer postradiotherapy-patient. Theyfounded that 5 years integer survival rates of low and high COX-2express tumor are 75% and 35% respectively, so COX-2 can be oneof index of uterine cervix cancer prognosis.Uterine cervix cancer has been the second death reason ofwomen tumor patient and its etiopathogenisis are still unclear.COX-2 participates the formation, development, and metabasis ofuterine cervix cancer through multiple ways. The studies aboutCOX-2 are helpful to reveal the mechanism of uterine cervixcarcinogenesis. Our results support the present hypothesis thatCOX-2 participates the formation, development and metabasis ofuterine cervix cancer, and it gradually increased following theadvancement and metabasis of uterine cervix cancer. In clinic,detecting COX-2 level before operation selectively profits moresuitable treatment and prognosis judgement. At present, COX-2selective inhibitor has been used in clinic tumor chemoprevention.Accompany with the profound research, there will be more theorybasis for the manufacture of COX-2 selective inhibitor.The main creations are following:Although there have been internal and foreign reports aboututerine cervix cancer expressing COX-2, rare reports about thesignificant of COX-2 in precancerous change have been given. Inthis study, we detected the expression of COX-2 in chronic cervicitis,CIN and uterine cervix cancer change using immunohistochemicalmethod. The results show that COX-2 positive rate was graduallyincreased in chronic cervicitis→CIN→ uterine cervix cancer(,all thedifference are significant, P<0.05), which provided theory basis forCOX-2 selective inhibitor using in clinic tumor chemoprevention.Furthermore, we detected COX-2 protein expression and geneexpression using Western blotting and RT-PCR semi-quantitymethod, which provided quantization basis for early diagnosis ofuterine cervix cancer. In addition, we detected the protein expressionof MMP-9, caspase-3 and VEGF in uterine cervix cancer tissuethrough which we proved that COX-2 has positive correlation withMMP-9 and caspase-3, and COX-2 takes part in the formation ofuterine cervix cancer by increasing invasion ability of tumour cellsand inhibiting cell apoptosis. This study having researched the effectof COX-2 in the development of uterine cervix cancer and providedeffective evidence for COX-2 selective inhibitor using inchemoprevention as well as treatment possesses profound socialeffects and economic returns.