Background The aim of this study was to investigate the effect of human umbilical vein endothelial cells on epithelial-to-mesenchymal transition of the cervical cancer cell line SiHa by studying the Notch1/lysyl oxidase (LOX)/SNAIL1 pathway. Methods Monocultures of SiHa cells, SiHa cells containing a control sequence, and Notch1 -silenced SiHa cells, as well as co-cultures of human umbilical vein endothelial cells with SiHa cells and Notch1 -silenced SiHa cells, were established. The invasiveness of SiHa cells in each group was evaluated using a Transwell assay. The mRNA levels of E-cadherin and vimentin were detected using quantitative real-time polymerase chain reaction. The expression levels of the matrix metalloproteinases MMP-2 and MMP-9 were determined in SiHa cells using an immunofluorescence assay and the protein activity was detected by gelatin zymography. Changes in LOX, SNAIL1 and NOTCH1 expression in the SiHa cells in each group were detected using western blotting. Results Compared with monocultured SiHa cells, co-cultured SiHa cells showed a significant increase in their invasiveness and expression levels of vimentin, as well as of NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin was significantly reduced and protein activities of MMP-2 and MMP-9 were increased. Compared with SiHa, mono- and co-cultured NOTCH 1 -silenced SiHa cells showed significant reductions in their invasiveness and expression levels of vimentin, NOTCH 1, LOX, and SNAIL1, whereas their expression of E-cadherin significantly increased and protein activities of MMP-2 and MMP-9 decreased. Conclusion Co-culture with human umbilical vein endothelial cells promoted the epithelial-to-mesenchymal transition of SiHa cells by activating the NOTCH1/LOX/SNAIL1 pathway in SiHa cells, which enhanced their invasive and metastatic capacities. The results of this study may provide a new perspective on cervical cancer metastasis and a theoretical basis for clinical treatment.
Objectives Pseudolaric acid B (PAB) has been shown to inhibit the growth of various tumor cells, but the molecular details of its function are still unknown. This study investigated the molecular mechanisms by which PAB induces apoptosis in HeLa cells. Methods The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to investigate the effect of PAB treatment in various cervical cancer cell lines. Annexin V/propidium iodide staining combined with flow cytometry and Hoechst 33258 staining were used to assess PAB-induced apoptosis. Additionally, we performed bioinformatics analyses and identified a paired box 2 ( PAX2 ) binding site on the BAX promoter. We then validated the binding using luciferase and chromatin immunoprecipitation assays. Finally, western blotting assays were used to investigate PAB effect on the Wnt signaling and the involved signaling molecules. Results PAB promotes apoptosis and downregulates PAX2 expression in HeLa cells in a time- and concentration-dependent manner. PAX2 binds to the promoter of BAX and inhibits its expression; therefore, PAX2 inhibition is associated with increased levels of BAX , which induces apoptosis of HeLa cells via the mitochondrial pathway. Additionally, PAB inhibits classical Wnt signaling. Conclusion PAB effectively inhibits Wnt signaling and PAX2 expression, and increases BAX levels, which induce apoptosis in HeLa cells. Therefore, PAB is a promising natural molecule for the treatment of cervical cancer.
Background: Recurrent implantation failure (RIF) has been recognized to be a major obstacle to the successful application of artificial reproduction technologies. In this study, the trends in RIF research were examined through a bibliometric analysis evaluating relevant literature quantitatively and qualitatively.Methods: A total of 1,764 publications from 2000 to 2020 were downloaded from the Web of Science Core Collection (WoSCC). Relevant articles were searched using the term "recurrent implantation failure" and other synonyms of this term. Using Excel 2013, CiteSpace V, and VOSviewer 1.6.10 software, data extracted from the literature, including countries/regions, institutions, journals, keywords, and trends, were analyzed.Next, a clustered network was constructed based on 46,718 references cited by the 1,764 publications to determine the top 10 cocited articles. Results:The annual number of publications on RIF progressively increased over time. The highest number of publications were from the United States. Analysis of the cocited reference cluster showed that "endometrial injury", "platelet-rich plasma", "chronic endometritis" and "extracellular vesicles" were the hotspots in RIF research. Burst detection analysis of the top keywords showed that "hysteroscopy" and "improvement" are emerging research foci.Conclusions: This study clarifies the current research status and evolution of research in the field of RIF.New therapeutic interventions designed to improve pregnancy outcomes are the focus of current research and are expected to dominate future research in the field of RIF.
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