The Expression Of BMI-1,Caspase-8 In Ovarian Cancer And The Human Ovarian Cancer Cell Lines SKOV3,3AO

Objective: To investigate the expression of Bmi-1 protein and Caspase -8 protein in epithelial ovarian neoplasm with the difference of histology classifications,tumor grades and clinic stages,benign ovarian tumors and normal tissues,to discuss the relationship of the both;the expression difference of Bmi-1 protein and Caspase-8 protein in human ovarian cancer cell lines SKOV3 and 3AO treated with the different concentration Oxaliplatin,were to discuss the relationship between the Bmi-1,Caspase-8 protein expression and chemotherapeutical monitoring of ovarian cancer.It was to search the reliable tumor marker for early diagnosis,recurrence monitoring,therapeutic effect and prognosis judgment of ovarian cancer and to provid clinical test'evidence.Methods:1.A specific and sensitive immunohistochemical assay of streptomyci -n-active-biotin-peroxidase complex (SABC)was used to detect the express -ion of Bmi-1,Caspase-8 in paraffin-embedded sections of 60 cases of primary epithelia ovarian cancer,16 cases of epithelial benign ovarian tumors and 10 cases of normal ovarian tissues individual.Contrasted by know positive slices (carcinoma of the breast).The primary antibody was substituted by PBS solution for negative contrast.2.Thiazoly blue tetrazolium bromide method(MTT) was used to meas -ure the proliferation difference of the human ovarian cancer cell lines SKOV3 and 3AO treated with the different concentration Oxaliplatin.And the Inhibitory Concentration of 50%(IC50) was calculated.3.Immunohistochemical assay of streptomycin-active-biotin-peroxida -se complex (SABC),Reverse transcription-polymerase chain reaction technique (RT-PCR) respectively were used to detect the expression difference of Bmi-1 and Caspase-8 in human ovarian cancer cell lines SKOV3 and 3AO treated with or without Oxaliplatin.Results:1.The expression of Bmi-1 protein and Caspase-8 protein in epithelial ovarian neoplasm:⑴The positive expressions of Bmi-1 in epithelial ovarian cancers (68.3%,P<0.05) were significantly higher than those in benign ovarian tumors (37.5%) and normal tissues(10.0%) . The expressions of Bmi-1 protein was related with histology classifications and clinic stages:the expressions of Bmi-1 protein in serous cystadenocarcinom -a of the ovary was more significant than in mucimucinous adenomaous cystadenocarcinoma and in endometrioid carcinoma of the ovary(P<0.05) ,and increased with clinic stages increased(P<0.05) .However there was no significant relationship between the expressions of Bmi-1 protein and tumor grades (P>0.05).⑵The positive expressions of Caspase-8 in epithelial ovarian cancers (31.7%,P<0.05) were significantly lower than those in benign ovarian tumors (68.8%) and normal tissues (90.0%).The expressions of Caspase-8 protein was related with tumor grades and clinic stages :the expressions of Caspase-8 protein in well differentiated carcinoma tissue was more significant than in intermediate differentia -ted carcinoma tissue and in low differentiated carcinoma tissue (P<0.05) ,and decreased with clinic stages increased(P<0.05).However there was no significant relationship between the expressions of Caspase-8 protein and histology classifications (P>0.05).⑶The expressions of Bmi-1 protein and Caspase-8 protein were no statistical difference among ages,CA125 and abdominal dropsy(P>0.05).2.The effects of Oxaliplatin on proliferation in the human ovarian cancer cell lines SKOV3 and 3AO:Concentrations of Oxaliplatin from 3.125 to 50 ug/ml,it could inhibit the proliferation of the human ovarian cancer cell lines SKOV3 and 3AO,and the inhibition depended on the exposure dose and time and the effect reached its peak in 48～72h(P<0.001).3.The expression of Bmi-1 and Caspase-8 in human ovarian cancer cell lines SKOV3 and 3AO:the positive expressions of Bmi-1 and Caspase-8 were detected in human ovarian cancer cell lines SKOV3 and 3AO in treated with Oxaliplatin or without.The Bmi-1 expression in human ovarian cancer cell lines SKOV3 and 3AO treated with Oxaliplatin was lower than treated without Oxaliplatin(P<0.05).on the contrary,the expression of Caspase-8 in human ovarian cancer cell lines SKOV3 and 3AO treated with Oxaliplatin was higher than treated without Oxaliplatin (P<0.05).4.The relationship between Bmi-1 protein and Caspase-8 protein in epithelial ovarian neoplasm:the expression of Bmi-1 was negatively correlated with Caspase-8 in epithelial ovarian neoplasm (r=0.296, P<0.05).Conclusion:1.The positive expressions of Bmi-1 in epithelial ovarian cancers were significantly higher than those in benign ovarian tumors and normal tissues,which suggested that activation of Bmi-1 was involved in the origin and development of ovarian cancer.The expressions of Bmi-1 protein in serous cystadenocarcinoma of the ovary was more significant than in mucimucinous adenomaous cystadenocarcinoma and in endometrioid carcinoma of the ovary,and increased with clinic stages increase,Which to suggested that Bmi-1 gene could serve as molecular biological parameter of early diagnosis.However,there was no significant relationship between the expressions of Bmi-1 protein and tumor grades,which could be because of the small sample size,and need an advanced study to confirm.The expressions of Bmi-1 protein was no statistical difference among ages,CA125 and abdominal dropsy.2.The positive expressions of Caspase-8 in epithelial ovarian cancers were significantly lower than those in benign ovarian tumors and normal tissues,which suggested that inactivation of Caspase-8 was involved in the origin and development of ovarian cancer.The expressions of Caspase-8 protein in well differentiated carcinoma tissue was more significant than in intermediate differentiated carcinoma tissue and in low differentiated carcinoma tissue,and decreased with clinic stages increased.However there was no significant relationship between the expressions of Caspase-8 protein and histology classifications.Inactivation of Caspase-8 could serve as molecular biological parameter of early diagnosis.The expressions of Bmi-1 protein and Caspase-8 protein were no statistical difference among ages,CA125 and abdominal dropsy.3.The expression of Bmi-1 was negatively correlated with Caspase-8 in epithelial ovarian neoplasm.Activation of Bmi-1 and inactivation of Caspase-8 could suggest that abnormality tumor cell multiplication induced tumorigenesis.It need an advanced study to confirm that to detect both could serve as molecular biological parameter of early diagnosis for ovarian cancer.4.Concentrations of Oxaliplatin from 3.125 to 50 ug/ml,it could inhibit the proliferation of the human ovarian cancer cell lines SKOV3 and 3AO,and the inhibition depended on the exposure dose and time and the effect reached its peak in 48～72h.It was security that Oxaliplatin served as the experiment intervention study.5.The positive expressions of Bmi-1 was detected in human ovarian cancer cell lines SKOV3 and 3AO in treated with Oxaliplatin or without.The Bmi-1 expression in human ovarian cancer cell lines SKOV3 and 3AO treated with Oxaliplatin was lower than treated without Oxaliplatin,which could suggest that the available chemotherapy.The increased positive expressions of Bmi-1 might suggest the recurrence of ovarian cancer.6.The expression of Caspase-8 in human ovarian cancer cell lines SKOV3 and 3AO treated with Oxaliplatin was higher than treated without Oxaliplatin,which could suggest that the chemotherapy maybe active the Caspase-8 gene to induce apoptosis.The inactivation of Caspase-8 could suggest the recurrence of ovarian cancer.