Study On The Role Of Cyclooxygenase-2 In Cervical Carcinoma: Growth Inhibition Of Cervical Carcinoma Cells By Selective Cyclooxygenase-2 Inhibitor

Objectives: (1) To investigate the expression of COX-2 before and after neoadjvant chemotherapy.(2)To explore the correlation between the expression of COX-2, PCNA, BCL-2 and the chemotherapy sensitivity. (3)To study the effect and mechanism of selective COX-2 inhibitor SIN on cervical carcinoma cells, and to explore its synergistic effect with carboplatin on cervical carcinoma cells.Methods (1) There are 31 patients with cervical cancer FIGO stageⅠb toⅡb treated with NACT. The expression of COX-2, PCNA, BCL-2 were detected by S-P immunohistochemistry technique. Statistical Analysis was used to check the relationship among them. (2)Collecting the clinical data to determine the correlation between COX-2, PCNA, BCL-2 and chemotherapy sensitivity. (3) MTT assay was used to determine the anti-proliferative effect of selective COX-2 inhibitor SIN and combination with carboplatin on cervical carcinoma cells. (4)The cell cycle distribution and apoptosis were detected by Flow cytometry.Results: (1) After intravenous NACT, 9.7% of patients (3/31) with complete remission and 54.8% of patients (17/31) with partial remission were recorded, and the total clinical response ratio of NACT was 64.5%, compared with 35.5% of patients with stable disease. (2)The expression of COX-2, PCNA decreased significantly after intravenous NACT, but no significant decrease occurred to the BCL-2 expression. (3) In complete remission cases and partial remission cases to NACT, the expression of COX-2 and PCNA after NACT were significantly decreased than that of the pretreatment cases, p＜0.05; A little decrease was found in stable disease cases but without significance, p＞0.05. However, the expression of BCL-2 showed no change in all cases. (4) There was significant relationship between the expression of COX-2 and PCNA, BCL-2 in those patients before NACT, p＜0.05. (5) MTT assays showed that selective COX-2 inhibitor SIN inhibited the growth of cervical carcinoma cells by concentration and time dependent, and synergistic effect appeared when combined with carboplatin. (6) Flow cytometry results demonstrated that the cell cycle was redistributed: the G1-Phase cell fraction was conspicuous increased while the S-Phase cell fraction was significantly decreased after the cells were treated with SIN (p＜0.05) However, the result was opposite after treated with carboplatin. When treated with both of them, G1-Phase and S-Phase cell fraction were between the values of single agent. Both of SIN and carboplatin could induce apoptosis in cervical carcinoma cells, while in a time and dose dependent way in SIN. The apoptotic index were significantly increased after treated with SIN combined with carboplatin.Conclusions: (1) The expression of COX-2 and PCNA were significantly deceased after NACT in cervical cancer and significantly correlate to the response to NACT, which suggests that COX-2 and PCNA could serve as markers to evaluate the effect of NACT. (2)There were significant relationship between the expression of COX-2 and PCNA, BCL-2, which indicates that COX-2 may promote the development of cancer through facilitating the proliferation and inhibiting the apoptosis of cervical carcinoma cells. (3) Selective COX-2 inhibitor SIN inhibited the growth of cervical carcinoma cells by concentration and time dependent, the mechanism of which may relates to its cell cycle arrest and apoptosis induction on cervical carcinoma cells. (4) The apoptotic index was significantly increased after treated with SIN combined with carboplatin, suggesting that the combination of them could exert synergistic antiproliferative effect on cervical carcinoma cells through influencing cell cycle distribution and apoptosis.