The Expression And Biological Significance Of Ref-1 And Caspase-3 In Cervical Carcinoma

Ref-1 gene (apurinic/apyrimidinic endonuclease) is also called redox factor-1. It is a multi-function limiting velocity enzymes of DNA base excision repair, also is the important repair factor result from the cell DNA radioactive and alkylatine agent. Through the base excision repair, Ref-1 is able to repair many purine-pyrimidine absence site in cell. This absence site has cell-toxin and gene-toxin, If not to be repaired it will result in mutation, chromosome unsteady, or apoptosis. Otherwise Ref-1 has reduction-oxidation function, keep multifarious transcription factor active, and participate in cell reaction, such as oxidation-stress, transcription factor regulation cell cucle control and apoptosis. Caspase-3 is called apoptosis factor, after activated analyze protein that related to apoptosis. So its activated is very important in apoptosis and signal transduction.This study detect the expression of Ref-1 and Caspase-3 in normal cervix and cervical squamous cell carcinoma by immunohistochemistry and RT-PCR methods, to investigate the relationship between expression of Ref-1 and Caspase-3 with pathological grades of cervical squamous cell carcinoma, to analyse their use and significance in carcinogenesis and metastasis of cervical carcinoma.Results:(1) The expression of Ref-1 were found no significant differences in normal cervix and well-differentiated cervical squamous carcinoma; following pathological grades up, the expression of Ref-1 down-regulation obviously. RT-PCR showed the expression of Ref-1 mRNA were found no significant differences in normal cervix and well-differentiated cervical squamous carcinoma, but the significant differences were found in normal cervix, moderately and poorly differentiated cervical squamous carcinoma. The expression of Ref-1 mRNA down-regulated following the up of pathological grades.(2) Much positive particles of Caspase-3 protein were found in normal cervix, the expression site of positive particles mainly in cell nucleus and its surrounding, cytolymph. The significant differences were found in normal cervix and cervical squamous carcinoma, and the expression of Caspase-3 down-regulated following up of pathological grades, the significant differences were found in each grades. RT-PCR showed no significance difference were found between normal cervix with well-differentiated cervical carcinoma, but the significance differences were found in normal cervix, moderated-differentiated and poorly-differentiated cervical carcinoma.Conclusion: The expression of Ref-1 gene and encodes protein down- regulated obviously in cervical squamous carcinoma, demonstrate Ref-1 gene inactivation is related to infiltration and metastasis, and the expression of Ref-1 also related to differentiation of cervical squamous carcinoma. The expression of Caspase-3 is down-regulated in cervical squamous carcinoma, demonstrate the weak expression of Caspase-3 maybe decreased apoptosis of cancer cell in infiltrate site, enhances the infiltration and metastasis ability of tumor. Caspase-3 selective stimulator maybe use for prevention and therapy to cervical carcinoma.