Cyclooxygenase Inhibitors And Cervical Cancer Relationship

Object:(1)To investigate the expression of COX-1 and COX-2 in cervical carcinoma,CIN and normal cervical epithelium. To evaluate the correlation between the COXs and clinico-pathologic variables in these cervical carcinoma patients.(2)To investigate the relationship between COX-2 and Ki-67 proliferation indexs, bax, microvascular density ( MVD ) and CD44v6 respectively. (3)To study the inhibitory effects of celecoxib, a selective cyclooxygenase-2 inhibitor, and aspirin, a non-selective cyclooxygenase inhibitor on two cervical carcinoma cell lines in vitro. Methods:(1)The expression of COX-1, COX-2, were examined by immunohistochemistry PV method and tissue chip method in 101 cases of cervical carcinomas ,12 cases of CIN and 10 cases of normal cervical epithelium;Ki-67, bax, MVD (labelled by CD34) and CD44v6 were examined in 101 cases of cervical carcinomas at the same time(.2)The effect of cell cycle and cell apoptotic rates were analyzed by flow cytometry (FCM). Results:(1)The positive expression rates of COX-1 have no significant difference between cervical carcinomas, CIN and normal cervical epithelium. COX-2 protein can not be detected in normal cervical epithelium; The positive expression rates of COX-2 in CIN (66.7%) and cervical carcinomas (87.1%) were significantly higher than in normal cervical epithelium(P<0.01),but there was no significant difference between CIN and cervical carcinomas(P>0.05).(2)The expression of COX-1 in cervical carcinomas has no correlation with age, clinical stages, grades ,invasion deep and metastasis of lymphatic node; The expression of COX-2 in cervical carcinomas has no correlation with age, clinical stages, grades and invasion deep, but it has a correlation with metastasis of lymphatic node(p<0.05)(.3)The expression of COX-2 in cervical carcinomas has positive correlation with Ki-67, MVD and CD44v6, but has no correlation with bax.(4)By FACS, it was found that the cell cycles of Hela and Siha cells were blocked by either aspirin and celecoxib, with the increasing of concentration: the G0/G1 phase ratio of Siha /Hela were increased ,the S phase ratio were inhibited and the G2～M phase ratio were not effected significantly. When incubated with aspirin(≥5mmol/L)/celecoxib( ≥10μmol/L) for 72 hours, the proliferation indexes (PI) were reduced(p<0.05), while the apoptotic rates were increased(p<0.05), we can find sub- G1 summit in FACS graph. Conclusion:(1)COX-1 probably has no significant relationship with carcinogenesis and development of cervical cancer; COX-2 may play an important role in carcinogenesis and development of cervical cancer, COX-2 may be valuable to further understand the biological behavior of cervical carcinoma.(2)The probable mechanisms were related with neovascularization, cell proliferation and cell adherence, but not related with the expression of bax. (3)Both aspirin and celecoxib inhibited the proliferation and induced the apoptosis of Siha and Hela cell lines in vitro.