贵州省人民医院妇科;
目的 探究黏结蛋白聚糖2(SDC2)是否可通过调控铁死亡影响宫颈癌细胞增殖、侵袭、迁移及其可能的作用机制。方法 培养正常宫颈上皮细胞H8、宫颈鳞状癌细胞C33A,分为H8组与C33A组。培养C33A细胞，分为对照组、低表达SDC2组、低表达SDC2+铁死亡抑制剂(ferrostation-1)组与低表达SDC2+铁死亡诱导剂(erastin)组。Western blot检测细胞中SDC2、溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化酶4(GPX4)蛋白。RT-qPCR检测C33A细胞中SDC2 mRNA水平。ELISA试剂盒检测C33A细胞中活性氧(ROS)、谷胱甘肽(GSH)、亚铁离子(Fe2+)水平。平板克隆检测C33A细胞克隆能力。划痕实验检测C33A细胞迁移能力。Transwell实验检测C33A细胞侵袭能力。结果 与H8组比较，C33A组细胞中SDC2、SLC7A11、GPX4蛋白及mRNA表达增加(P<0.05)。与对照组比较，低表达SDC2组C33A细胞增殖、迁移及侵袭能力降低(P<0.05),C33A细胞中SLC7A11、GPX4蛋白及mRNA表达减少(P<0.05),GSH水平减少，ROS及Fe2+水平增加(P<0.05)。与低表达SDC2组比较，低表达SDC2+ferrostation-1组SLC7A11、GPX4蛋白及mRNA表达增加(P<0.05),GSH水平增加，ROS及Fe2+水平减少(P<0.05)。与对照组比较，低表达SDC2+erastin组C33A细胞增殖、迁移及侵袭能力降低(P<0.05)。结论 SDC2在C33A宫颈癌细胞中表达增加，低表达SDC2可激活SLC7A11/GPX4通路介导的铁死亡，从而降低C33A细胞的增殖、侵袭及迁移能力。
| 223 | 0 | 66 |
| 下载次数 | 被引频次 | 阅读次数 |
[1] Ginsburg O,Bray F,Coleman M P,et al.The global burden of women′s cancers:a grand challenge in global health[J].Lancet,2017,389(10071):847-60.doi:10.1016/S0140-6736(16)31392-7.
[2] Da Costa A M,Hashim D,Fregnani J H T G,et al.Overall survival and time trends in breast and cervical cancer incidence and mortality in the Regional Health District (RHD) of Barretos,Sao Paulo,Brazil[J].BMC Cancer,2018,18(1):1079.doi:10.1186/s12885-018-4956-7.
[3] Hua R,Yu J,Yan X,et al.Syndecan-2 in colorectal cancer plays oncogenic role via epithelial-mesenchymal transition and MAPK pathway[J].Biomed Pharmacother,2020,121:109630.doi:10.1016/j.biopha.2019.109630.
[4] Zhao G,Ma Y,Li H,et al.A novel plasma based early colorectal cancer screening assay base on methylated SDC2 and SFRP2[J].Clin Chim Acta,2020,503:84-89.doi:10.1016/j.cca.2020.01.010.
[5] Ma N,Li X,Wei H,et al.Circular RNA circNFATC3 acts as a miR-9-5p sponge to promote cervical cancer development by upregulating SDC2[J].Cell Oncol (Dordr),2021,44(1):93-107.doi:10.1007/s13402-020-00555-z.
[6] Jiang X,Stockwell B R,Conrad M.Ferroptosis:mechanisms,biology and role in disease[J].Nat Rev Mol Cell Biol,2021,22(4):266-82.doi:10.1038/s41580-020-00324-8.
[7] Zhao M Y,Liu P,Sun C,et al.Propofol augments paclitaxel-induced cervical cancer cell ferroptosis in vitro[J].Front Pharmacol,2022,13:816432.doi:10.3389/fphar.2022.816432.
[8] Sharma S,Deep A,Sharma A K.Current treatment for cervical cancer:an update.[J] Anticancer Agents Med Chem,2020,20(15):1768-79.doi:10.2174/1871520620666200224093301.
[9] Ward Z J,Grover S,Scott A M,et al.The role and contribution of treatment and imaging modalities in global cervical cancer management:survival estimates from a simulation-based analysis[J].Lancet Oncol,2020,21(8):1089-98.doi:10.1016/S1470-2045(20)30316-8.
[10] Cancer Genome Atlas Research Network,Albert Einstein College of Medicine,Analytical Biological Services.Integrated genomic and molecular characterization of cervical cancer[J].Nature,2017,543(7645):378-84.doi:10.1038/nature21386.
[11] Chen C,Shen N,Chen Y,et al.LncCCLM inhibits lymphatic metastasis of cervical cancer by promoting STAU1-mediated IGF-1 mRNA degradation[J].Cancer Lett,2021,518:169-79.doi:10.1016/j.canlet.2021.07.005.
[12] Cohen P A,Jhingran A,Oaknin A,et al.Cervical cancer[J].Lancet,2019,393(10167):169-82.doi:10.1016/S0140-6736(18)32470-X.
[13] Yue C,Zhang Y,Wang Y,et al.The application value of syndecan-2 gene methylation for colorectal cancer diagnosis:a clinical study and meta-analyses[J].Front Med (Lausanne),2022,9:753545.doi:10.3389/fmed.2022.753545.
[14] Santos N J,Barquilha C N,Barbosa I C,et al.Syndecan family gene and protein expression and their prognostic values for prostate cancer[J].Int J Mol Sci,2021,22(16):8669.doi:10.3390/ijms22168669.
[15] Tsoyi K,Osorio J C,Chu S G,et al.Lung adenocarcinoma syndecan-2 potentiates cell invasiveness[J].Am J Respir Cell Mol Biol,2019,60(6):659-66.doi:10.1165/rcmb.2018-0118OC.
[16] Santos N J,Barquilha C N,Barbosa I C,et al.Syndecan family gene and protein expression and their prognostic values for prostate cancer[J].Int J Mol Sci,2021,22(16):8669.doi:10.3390/ijms22168669.
[17] Li J,Lu K,Sun F,et al.Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway[J].J Transl Med,2021,19(1):96.doi:10.1186/s12967-021-02745-1.
[18] Lei G,Zhuang L,Gan B.Targeting ferroptosis as a vulnerability in cancer[J].Nat Rev Cancer,2022,22(7):381-96.doi:10.1038/s41568-022-00459-0.
[19] Chang X,Miao J.Ferroptosis:mechanism and potential applications in cervical cancer[J].Front Mol Biosci,2023,10:1164398.doi:10.3389/fmolb.2023.1164398.
基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.02.007
中图分类号:R737.33
引用信息:
[1]姚雪芹,肖雪莲,罗其英等.SDC2表达调控铁死亡参与宫颈癌发生的作用及机制[J].安徽医科大学学报,2025,60(02):234-239.DOI:10.19405/j.cnki.issn1000-1492.2025.02.007.
基金信息:
贵州省卫生健康科研基金项目(编号：GZ20HDF154)~~