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Fraxetin suppresses the proliferation, migration, and invasion of ovarian cancer cells by inhibiting the TLR4/STAT3 signaling pathway. 2023

Ruhu Xu, and Yingdan Ruan, and Lan Zhang, and Yating Gu, and Mingming Liu
Department of Traditional Chinese Medicine, Taizhou First People's Hospital, Taizhou City, China.

Little therapeutic effect can be exerted on malignant ovarian cancer at the terminal period. Traditional Chinese medicine (TCM) has been a potential way for the treatment of various diseases. In this research, we probed into the potential curative effect of Fraxetin (FXT), a TCM monomer, on ovarian cancer. Ovarian cancer cells were treated with FXT at different concentrations for 12 h, or pretreated by 0.5 μM of colivelin, a STAT3 activator, for 1 h and then treated with 80 μM of FXT for 12 h. The viability of ovarian cancer cells was measured by MTT assay, and the cell colony number was counted after colony formation assay. Transwell assay was conducted for investigating the relationship between the FXT at different concentrations and the invasion as well as migration rates of ovarian cancer cells. The expressions of epithelial-to-mesenchymal transition (EMT)-associated markers and TLR4/STAT3 signaling pathway-related proteins in ovarian cancer cells after the treatment of FXT were measured by western blot. FXT inhibited the viability, invasion, migration, and proliferation of SKOV3 and SW626 cells and suppressed EMT, but colivelin reversed the impacts of FXT. FXT also suppressed the expressions of N-cadherin, snail, vimentin, TLR4, phosphorylated (P)-STAT3, cyclin D1, and C-myc, whilst promoting that of E-cadherin by inhibiting the activation of TLR4/STAT3 signaling pathway. FXT exerts a therapeutic effect on ovarian cancer by repressing the TLR4/STAT3 signaling pathway. With the accumulating concentrations of FXT, the therapeutic effect becomes more and more obvious.

UI MeSH Term Description Entries
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D050796 STAT3 Transcription Factor A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130. APRF Transcription Factor,Acute-Phase Response Factor,IL6-Response Factor,LIF-Response Factor,STAT3 Protein,STAT3a Transcription Factor,STAT3b Transcription Factor,Signal Transducer and Activator of Transcription 3,Stat3alpha Transcription Factor,Stat3beta Transcription Factor,Acute Phase Response Factor,IL6 Response Factor,LIF Response Factor,Response Factor, Acute-Phase,Transcription Factor, APRF,Transcription Factor, STAT3,Transcription Factor, STAT3a,Transcription Factor, STAT3b,Transcription Factor, Stat3alpha,Transcription Factor, Stat3beta
D051197 Toll-Like Receptor 4 A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA. TLR4 Receptor,Toll-4 Receptor,Receptor, TLR4,Toll 4 Receptor,Toll Like Receptor 4
D058750 Epithelial-Mesenchymal Transition Phenotypic changes of EPITHELIAL CELLS to MESENCHYME type, which increase cell mobility critical in many developmental processes such as NEURAL TUBE development. NEOPLASM METASTASIS and DISEASE PROGRESSION may also induce this transition. Epithelial-Mesenchymal Transformation,Epithelial Mesenchymal Transformation,Epithelial Mesenchymal Transition,Transformation, Epithelial-Mesenchymal,Transition, Epithelial-Mesenchymal

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