Regulation mechanism of chaetocin on invasion and migration of ovarian cancer cells
Objective To investigate the effects of chaetocin on the migration and invasion of ovarian cancer cells and explore the potential mechanisms based on thioredoxin reductase-1(TrxR1)and NF-κB pathway in order to find and verify the possible anti-cancer properties of trichodermin.Methods Ovarian cancer cell lines SK-OV-3 and OVCAR-3 were cultured and treated with chaetocin.Cell viability and IC50 of chaetocin were analyzed by CCK-8 assay,while the cell toxicity was verified by EdU staining.The cells were divided into six groups,including chaetocin 0 μm group,chaetocin 8 μm group,physiological saline + chaetocin 0 μm group,physiological saline + chaetocin 8 μm group,NF-κB activator 1+ chaetocin 0 μm group,and NF-κB activator 1+ chaetocin 8 μm group.The cell migration rate was measured by in vitro cell wound healing assay,while the cell invasion rate was assessed by Transwell cell invasion assay.The expression of TrxR1 mRNA was detected by qRT-PCR.Western blotting was used to detect the expression of NF-κB in cytoplasm and nucleus,as well as the expression of TrxR1,p-NF-κB,p-IKKα/β,and p-IκBα in the whole cell.Results Chaetocin had a strong inhibitory effect on the viability of ovarian cancer cells.The IC50 of chaetocin on SK-OV-3 and OVCAR-3 cells at24 h were(72.92±9.18)and(61.28±8.56)μm,respectively.The maximum non-toxic dose of chaetocin was8 μm.Compared with the chaetocin 0 μm group,chaetocin 8 μm group inhibited the migration and invasion of SK-OV-3 and OVCAR-3 cells,and significantly down-regulated the expression of TrxR1,p-NF-κB,p-IKKα/β,and p-IκBα.Compared with the physiological saline + chaetocin 8 μm group,the NF-κB activator 1+ chaetocin 8 μm group significantly promoted the migration and invasion of SK-OV-3 and OVCAR-3 cells,and up-regulated the expression of TrxR1,p-NF-κB,p-IKKα/β,and p-IκBα.Conclusion Chaerocin inhibits the proliferation and expression of TrxR1 in ovarian cancer and reduces the invasion and migration of ovarian cancer cells by inhibiting the activation of NF-κB pathway.
chaetocinthioredoxin reductase-1NF-κBovarian cancer cellsinvasionmigration
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