| Background and objective Ovarian cancer is one of the most common malignancy of genitourinary system in female worldwide, the morbidity of which ranks the third after squamous-cell cervical carcinoma(SCCC) and endometrial cancers, but the mortality of which moves up to the first place accounting for approximately 65%, and more than half of the female patients diagnosed with ovarian cancer died from this disease, mostly from disease recurrence of progression on therapy. Epithelial ovarian cancer(EOC) is the most common pathological type of ovarian neoplasms with the propotion of 85%—90%, and this type is highly lethal. The 5-year survival rate is still poor, although 70% of female patient with advanced-stage epithelial ovarian cancer initially respond to surgical debunking and standard chemotherapy, probably due to the aggressive metastasis within the peritoneal cavity, a subset of cells being resistant to chemotherapy or the complexity of embryonic development, histological anatomy and endocrine function in ovarian. Therefore, research of the etiology and pathogenesis of epithelial ovarian cancer makes a big difference to the clinical therapy of ovarian neoplasms.Aspirin is a common non-steroiadal anti-inflammatory drug, which is frequently used in clinical therapy of osteoarthritis, rheumatoid arthritis, fever and pain,arteriovenous thrombosis, coagulation disorders and so on, but the specific molecular mechanism is still not clear. Furthermore, aspirin has a positive meaning on prevention and treatment in a variety of human tumor diseases, whose huge potential in the study of anti-tumor should be arouse extensive attention.SOX7 gene, a member of subfamily SOXF which belongs to SOX family along with SOX17 and SOX18, is located at the chromosomal region of 8p23.1 including two exons and one intron, and encodes a small molecular protein which contains 377 amino acid residue and contains a HMG domain with strong amino acid similar to the HMG domain of sex-determining region Y(SRY). SOX7 plays an important role in many biological processes such as embryonic development and endoderm differentiation. Alleles drop-out in the chromosomal region of 8p is one of most common genetic changes in cells, and inactivation of tumor suppressor gene caused by alleles drop-out is the main inducement of cancers. Thus we conjecture that SOX7 gene probably plays as a tumor suppressor in the occurrence and development of tumors. Wnt/β-catenin signaling with a high evolutionary conservation is the most common signal pathway regulated by Wnt, the mechanism of which is relatively clear. Wnt/β-catenin signaling plays an important regulatory role in the occurrence and development of many human diseases especially for tumors. The gene silencing, gene mutation or gene deletion in Wnt/β-catenin signaling may induce aberrant activation,and the occurrence of tumors at last. SOX7 gene probably plays a key role in many biological processes such as proliferation, development and apoptosis in tumor cells by regaluting Wnt/β-catenin signaling, but the mechanism is still unknown. Furthermore, the expression levels, molecular mechanisms and the relationship of SOX7 gene and Wnt/β-catenin signaling in epithelial ovarian cancer have received less attention.In this study, expression levels of SOX7, β-catenin and cyclinD1 in tumor tissues and normal tissues were detected by quantitative real-time PCR; human epithelial ovarian cancer SKOV3 cells were treated with different concentrations of Aspirin in vitro and expression variation of SOX7, β-catenin and cyclin D1 in SKOV3 cells were detected by quantitative real-time PCR; the effect of Aspirin on SKOV3 cells proliferation was measured by MTT assay, and the inhibition rate was calculated.To research the possible pathogenetic mechanism of SOX7 and Wnt/β-catenin signaling in epithelial ovarian cancer.Methods(1) Expression levels of SOX7, β-catenin and cyclin D1 in tumor tissues and normal tissues were detected by quantitative real-time PCR, and the result was calculated by 2-ΔΔCT method.(2) Human epithelial ovarian cancer SKOV3 cells were treated with different concentrations of Aspirin(0 mmol/L, 0.5 mmol/L, 1 mmol/L, 2 mmol/L, 3 mmol/L) in vitro and expression variation of SOX7, β-catenin and cyclin D1 in SKOV3 cells were detected by quantitative real-time PCR, and the result was calculated by 2-ΔΔCT method.(3) The effect of Aspirin on SKOV3 cells proliferation was measured by MTT assay, and the inhibition rate was calculated. SPSS Statistics software version 19.0 was used for the statistical analysis. Continuous data are presented as mean ± SD, independent-samples t-test was used to compare two groups of continuous variables, one-way analysis of variance(ANOVA) was used to compare more than two groups of continuous variables, least significant difference test(LSD-t) was used to compare between any two groups, Nonparametric test was used for comparation of non-normal distribution data, Pearson correlation was used to analysis the correlation between two variables. A level of P < 0.05 was considered statistically significant.Results 1 Expression levels of SOX7, β-catenin and cyclin D1 in tumor tissues and normal tissues: Expression levels of SOX7, β-catenin and cyclin D1 in tumor tissues and normal tissues respectively were: SOX7,6.102±0.781 vs 1.701±1.104, t=3.614, P=0.001;β-catenin,2.312±0.267 vs 9.214±0.351, t=13.651, P<0.001;cyclin D1,3.021±0.981 vs 6.701 ± 1.216, t=5.967, P<0.001. The differences were statistically significance. 2 Expression variation of SOX7, β-catenin and cyclin D1 in SKOV3 cells after stimulated by Aspirin: After stimulation of Aspirin, expression level of SOX7 was increased in the course of concentrations(0.725±0.101 vs 0.947±0.011 vs 1.923±0.126 vs 2.857±0.218 vs 4.402±0.086,F=12.151,P<0.001) but the results of β-catenin and cyclin D1 were decreased as the concentrations of Aspirin increasing(β-catenin:1.759±0.334 vs 1.644±0.645 vs 0.963±0.553 vs 0.705±0.618 vs 0.643±0.539,F=6.214,P<0.001;cyclin D1:2.313±0.142 vs 2.144±0.055 vs 1.542±0.033 vs 0.941±0.018 vs 0.323±0.012,F=4.903,P<0.001). The differences were statistically significance. 3 The correlation among the expressions of SOX7, Cyclin D1 and β-catenin after stimulated by different concentrations of Aspirin: After stimulation of Aspirin, expression level of SOX7, β-catenin have a significance correlation(r=-0.983, P<0.05), expression level of SOX7, cyclin D1 have a significance correlation(r=-0.978, P<0.05), expression level of cyclin D1, β-catenin have a significance correlation(r= 0.986, P<0.05). The differences were statistically significance. 4 Influence of Aspirin on cell proliferation of human epithelial ovarian cancer SKOV3 cells: Aspirin has a significant inhibition on cell proliferation activity of human epithelial ovarian cancer SKOV3 cells with a concentration-dependent manner. The inhibition of cell proliferation activity grew with the increase of concentration of Aspirin(0 vs 0.935±0.065 vs 11.784±2.743 vs 20.192±3.441 vs 32.462±5.821,F=20.481,P<0.001). The differences were statistically significance.Conclusions(1) SOX7 perhaps plays a role of tumor suppressor gene in the pathogenesis ofEOC, and there exists abnormal activation of Wnt/β-catenin signaling in EOC.(2) Aspirin significantly upregulates expression levels of SOX7, downregulates expression levels of β-catenin and cyclin D1, inhibits cell proliferation and induces apoptosis in human epithelial ovarian cancer SKOV3 cells.(3) SOX7 gene maybe a negative regulator of Wnt/β-catenin signaling. |
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