毛壳素对卵巢癌细胞侵袭和迁移的调控机制研究  

Regulation mechanism of chaetocin on invasion and migration of ovarian cancer cells

作　　者：吴伟权 苏裕东 萧丽娟[1] 陈艳雅[1] Wu Weiquan;Su Yudong;Xiao Lijuan;Chen Yanya(Department of Obstetrics and Gynecology,Dongguan Peoples Hospital,Dongguan Guangdong 523000,P.R.China)

机构地区：[1]东莞市人民医院妇产科,广东东莞523000

出　　处：《中国计划生育和妇产科》2024年第4期47-51,58,F0004,共7页Chinese Journal of Family Planning & Gynecotokology

基　　金：广东省医学科学技术研究基金项目(项目编号:A2021085)。

摘　　要：目的体外研究毛壳素(chaetocin)对卵巢癌细胞迁移和侵袭的影响,并通过探讨硫氧还蛋白还原酶-1(TrxR1)和NF-κB通路的作用机制以期发现并验证毛壳素可能的抗癌属性。方法培养卵巢癌细胞系SK-OV-3和OVCAR-3,用毛壳素处理卵巢癌细胞,用CCK-8法分析毛壳素的细胞毒性和IC50,用EdU染色验证毛壳素的细胞毒性。将细胞分为6组,包括毛壳素0μm组、毛壳素8μm组、生理盐水+毛壳素0μm组、生理盐水+毛壳素8μm组、NF-κB激活剂1+毛壳素0μm组、NF-κB激活剂1+毛壳素8μm组。体外细胞伤口愈合实验检测细胞迁移率。Transwell细胞侵袭实验检测细胞侵袭率。qRT-PCR检测TrxR1 mRNA的表达。Western blot检测细胞质和细胞核中NF-κB的表达及检测全细胞中TrxR1、p-NF-κB、p-IKKα/β和p-IκBα的表达。结果毛壳素对卵巢癌细胞增殖有较强的抑制作用。毛壳素24 h对SK-OV-3和OVCAR-3细胞的IC50分别为(72.92±9.18)μm和(61.28±8.56)μm。8μm毛壳素为无细胞毒性的最大剂量。与毛壳素0μm组比,毛壳素8μm组抑制了SK-OV-3和OVCAR-3细胞的迁移和侵袭,并显著下调TrxR1、p-NF-κB、p-IKKα/β和p-IκBα的表达。与生理盐水+毛壳素8μm组比,NF-κB激活剂1+毛壳素8μm组显著促进了SK-OV-3和OVCAR-3细胞的迁移和侵袭,并显著上调了TrxR1、p-NF-κB、p-IKKα/β和p-IκBα的表达。结论毛壳素抑制卵巢癌细胞的增殖和TrxR1的表达,并通过抑制NF-κB通路的激活减少卵巢癌细胞的侵袭和迁移。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-kB pathway in order to find and verify the possible anticancer properties of trichodermin.MethodssOvarian cancer cell lines SK-OV-3 and OVCAR-3 were cultured and treated with chaetocin.Cell viability and ICso 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 Oμm group,chaetocin 8μm group,physiological saline+chaetocin Oμm group,physiological saline+chaetocin 8μm group,NF-kB activator 1+chaetocin Oμm group,and NF-kB activator 1+chaetocin 8μm 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 TrxRI mRNA was detected by qRT-PCR.Western blotting was used to detect the expression of NF-kB in cytoplasm and nucleus,as well as the expression of TrxR1,p-NF-kB,p-IKKo/β,and p-IkBαin the whole cell.ResultsChaetocin had a strong inhibitory effect on the viability of ovarian cancer cells.The ICso of chaetocin on SK-OV-3 and OVCAR-3 cells at 24 h were(72.92±9.18)and(61.28±8.56)μm,respectively.The maximum non-toxic dose of chaetocin was 8μm.Compared with the chaetocin Oμm group,chaetocin 8μm group inhibited the migration and invasion of SK-OV-3 and OVCAR-3 cells,and significantly down-regulated the expression of TrxR1,p-NF-kB,p-IKKo/β,and p-IkBα.Compared with the physiological saline+chaetocin 8μm group,the NF-kB activator 1+chaetocin 8μm group significantly promoted the migration and invasion of SK-OV-3 and OVCAR-3 cells,and up-regulated the expression of TrxR1,p-NF-kB,p-IKKo/β,and p-IkBα.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-kB pathway.

关 键 词：毛壳素 硫氧还蛋白还原酶-1 核因子-ΚB 卵巢癌细胞 侵袭 迁移 

分 类 号：R737.31[医药卫生—肿瘤]