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Objective@#To determine whether bisphenol S (BPS), a common substitute for bisphenol A (BPA), induces cell proliferation and migration in human endometrial epithelial cells (Ishikawa) and adult mouse uterine tissues.@*Methodology@#Human endometrial Ishikawa cells were exposed to low doses of BPS (1 nM and 100 nM) for 72 hours. Cell proliferation was assessed through the viability assays MTT and CellTiter-Glo®. Wound healing assays were also used to evaluate the migration potential of the cell line. The expression of genes related to proliferation and migration was also determined. Similarly, adult mice were exposed to BPS at a dose of 30 mg/kg body weight/day for 21 days, after which, the uterus was sent for histopathologic assessment.@*Results@#BPS increased cell number and stimulated migration in Ishikawa cells, in association with the upregulation of estrogen receptor beta (ESR2) and vimentin (VIM). In addition, mice exposed to BPS showed a significantly higher mean number of endometrial glands within the endometrium.@*Conclusion@#Overall, in vitro and in vivo results obtained in this study showed that BPS could significantly promote endometrial epithelial cell proliferation and migration, a phenotype also observed with BPA exposure. Hence, the use of BPS in BPA-free products must be reassessed, as it may pose adverse reproductive health effects to humans.
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Útero , HiperplasiaRESUMEN
@# Objective: To study the expression of H O X A 1 0 gene in endometrial carcinoma and its effect on the apoptosis, migration and invasion of Ishikawa cells. Methods: Twenty-one cases of endometrial carcinoma tissue samples and 25 cases of normal endometrial tissue samples from patients treated at the Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital from 2012 to 2013 were collected for this study. The mRNA and protein expressions of H O X A 1 0 in endometrial carcinoma and normal endometrial tissues were separately tested by Realtime-qPCR (qRT-PCR) and Western blotting. Ishikawa cells were infected with adenovirus-flagHOXA10 at different multiplicity (5, 10, 20 MOI), and infected by adenovirus-flag-lacz (20 MOI) as control; And the cell apoptosis was tested by Flow Cytometry. Ishikawa cells were transfected with 50 nmol/L si-HOXA10 plasmids and 50 nmol/L si-NC plasmids, as down-regulation group and down-regulation control group, respectively. Ishikawa cells were infected with 20 MOI adenovirus-flagHOXA10 and 20 MOI adenovirus-flag-lacz, as up-regulation group and up-regulation control group, respectively. The ability of migration and invasion was detected by transwell assay. Results: The results of qRT-PCR and Western blotting showed that the expressions of H O X A 1 0 mRNA and protein in endometrial carcinoma samples were both significantly lower than normal samples [mRNA: (0.56± 0.14)vs (1.36±0.33), P<0.01; protein: (1.01±0.25) vs (2.10±0.71), P<0.001]. After the up-regulation of H O X A 1 0 gene in Ishikawa cell line, the cell apoptosis rate in ad-flag-HOXA10 groups (5, 10, 20 MOI) was significantly raised, and most of which was in the early apoptosis [(50.92±8.79)%, (55.17±4.07)%, (76.10±3.65)% vs (7.74 ± 0.15)%, all P <0.01]. The number of migrated cells was markedly up-regulated in si-HOXA10 group [(248±25) vs (135±15), P <0.01] but markedly down-regulated in ad-flag-HOXA10 group [(50±6) vs (100±13), P <0.01]. The number of invasive cells was markedly up-regulated in si-HOXA10 group [(131±18) vs (66±9), P <0.01] but markedly down-regulated in ad-flag-HOXA10 group [(34±8) vs (60±4), P <0.01]. Conclusions: Both mRNAand protein expressions of H O X A 1 0 were down-regulated in endometrial carcinoma samples than in normal endometrium. Up-regulation of H O X A 1 0 gene in Ishi kawa cell line can promote cell apoptosis and inhibit cell migration and invasion.
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Objective To investigate the effect of cisplatin and 5-fluorouracil on endocrine Ishikawa cells in the treatment of endometrial cancer. Methods The human endometrial cancer cell line Ishikawa were selected, at the logarithmic growth period, the cells were divided into three groups of 5-fluorouracil (5 mg/L) group, cisplatin (5 mg/L) group and cisplatin (5 mg/L) combined with fluorouracil (5 mg/L) group ( combined group).After treated with corresponding drugs treatment, the cell viability was detected by MTT, the apoptosis was detected by flow cytometry, and the Bcl-2 and p65 expressions cells were detected by Western blot.Results The inhibitory rate of combined group, cisplatin group and 5-fluorouracil group were (41.45 ± 3.13)%, (25.20 ±3.09)% and (23.19 ±4.10)% respectively, and the inhibitory rate in the combined group was significantly higher than that of the other two groups (P<0.05).The apoptosis rate of the combined group, cisplatin group and 5-group were (29.44 ±4.35)%, (5.74 ±1.12)% and (5.82 ±1.78)% respectively, and the apoptosis rate in the combined group was significantly higher than that of the other two groups (P<0.05).The Bcl-2 relative expression in the combined group, cisplatin group and 5-fluorouracil group were (0.31 ±0.11), (1.23 ±0.49) and (1.28 ±0.59), the p65 expression were (0.67 ±0.23), (1.67 ±0.56) and (1.71 ±0.71), combined group of Bcl-2 and p65 relative expressions were obviously less than that of the other two groups ( P <0.05 ) .Conclusion Cisplatin combined with 5-fluorouracil on endocrine Ishikawa cells in the treatment of endometrial cancer could promote cell apoptosis, inhibit the cell proliferation, and its mechanism may be related to the inhibition of Bcl-2 and p65 protein expressions.