Ovarian cancer is a leading killer of women, and no cure for advanced ovarian cancer is available. Alisertib (ALS), a selective Aurora kinase A (AURKA) inhibitor, has shown potent anticancer effects, and is under clinical investigation for the treatment of advanced solid tumor and hematologic malignancies. However, the role of ALS in the treatment of ovarian cancer remains unclear. This study investigated the effects of ALS on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition (EMT), and the underlying mechanisms in human epithelial ovarian cancer SKOV3 and OVCAR4 cells. Our docking study showed that ALS, MLN8054, and VX-680 preferentially bound to AURKA over AURKB via hydrogen bond formation, charge interaction, and π-π stacking. ALS had potent growth-inhibitory, proapoptotic, proautophagic, and EMT-inhibitory effects on SKOV3 and OVCAR4 cells. ALS arrested SKOV3 and OVCAR4 cells in G2/M phase and induced mitochondria-mediated apoptosis and autophagy in both SKOV3 and OVCAR4 cell lines in a concentration-dependent manner. ALS suppressed phosphatidylinositol 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways but activated 5′-AMP-dependent kinase, as indicated by their altered phosphorylation, contributing to the proautophagic activity of ALS. Modulation of autophagy altered basal and ALS-induced apoptosis in SKOV3 and OVCAR4 cells. Further, ALS suppressed the EMT-like phenotype in both cell lines by restoring the balance between E-cadherin and N-cadherin. ALS downregulated sirtuin 1 and pre-B cell colony enhancing factor (PBEF/visfatin) expression levels and inhibited phosphorylation of AURKA in both cell lines. These findings indicate that ALS blocks the cell cycle by G2/M phase arrest and promotes cellular apoptosis and autophagy, but inhibits EMT via phosphatidylinositol 3-kinase/Akt/mTOR-mediated and sirtuin 1-mediated pathways in human epithelial ovarian cancer cells. Further studies are warranted to validate the efficacy and safety of ALS in the treatment of ovarian cancer.
This study aims to determine the difference between transcervical resection of septum (TCRS) and transcervical incision of septum (TCIS) in the improvement of reproductive prognosis. Study Design: Women with uterine septum in the Affiliated Hospital of Ningxia Medical University were retrospectively analyzed. A statistical method was used according to operative time, postoperative menstruation, postoperative pregnancy rate, postoperative term delivery rate, and so on. Results: Compared with TCRS, the TCIS method decreased operative time, blood loss, and consumption of uterus distension medium. No statistical difference was observed in operative complications between the two methods. After TCIS, the incidence of uterine adhesion was low and the degree of endometrial epithelialisation was high by hysteroscopy review. No statistical difference was observed in residual septum after the operation. The total pregnancy rate after TCIS was higher than that of TCRS. However, no statistical difference was observed in early and late pregnancy loss rates, preterm birth rate, and term birth rate. Conclusion: TCIS exhibits advantages of decreasing operative time, blood loss, and consumption of uterus distension medium. TCIS can reduce the incidence of uterine adhesion and can promote endometrial epithelialisation, which are the key factors to increase pregnancy rate after operation.
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