| 52 | 0 | 54 |
| 下载次数 | 被引频次 | 阅读次数 |
目的 探讨非红细胞血影蛋白-β2(SPTBN2)蛋白是否诱导人胃癌细胞发生铁死亡及其机制，以及对人胃癌细胞生物学行为的影响。方法 采用生物信息学、免疫组织化学、免疫细胞化学、Westernblot检测SPTBN2蛋白在人胃癌组织和人胃癌细胞中的表达。利用siRNA干扰技术下调人胃癌细胞中SPTBN2蛋白表达，分别利用可见分光光度法和荧光染色法检测铁死亡标志物丙二醛（MDA）和活性氧（ROS）的含量，利用Westernblot检测人胃癌细胞中核因子红系2相关因子2(Nrf2)蛋白表达，利用CCK-8、划痕损伤实验和Transwell侵袭实验检测人胃癌细胞的增殖、迁移和侵袭能力。结果 SPTBN2主要表达在细胞质中，与癌旁正常胃膜组织和人正常胃膜上皮细胞相比，SPTBN2蛋白在人胃癌组织和人胃癌细胞中呈高表达（P<0.05）。下调人胃癌细胞中SPTBN2后，铁死亡标志物MDA和ROS的含量显著增高（P<0.01），Nrf2蛋白的含量显著下降（P<0.05），人胃癌细胞增殖、侵袭和迁移能力显著下降（P<0.01）。结论 下调SPTBN2能够诱导人胃癌细胞发生铁死亡，抑制人胃癌细胞增殖、迁移和侵袭能力，且可能通过下调Nrf2蛋白诱导人胃癌细胞发生铁死亡。
Abstract：Objective To investigate whether non-erythrocyte haemoglobin-β2 ( SPTBN2) protein induces ferroptosis in human gastric cancer cells and its mechanism， as well as its effect on the biological behaviour of human gastric cancer cells. Methods Bioinformatics， immunohistochemistry， immunocytochemistry， and Western blot were used to detect the expression of SPTBN2 protein in human gastric cancer tissues and human gastric cancer cells. SPTBN2 protein expression was down-regulated in human gastric cancer cells using siRNA interference， the levels of ferroptosis markers malondialdehyde (MDA) and reactive oxygen species (ROS) were detected using visible spectrophotometry and fluorescence staining， respectively， nuclear factor red lineage 2-related factor 2 (Nrf2) protein expression was detected in human gastric cancer cells using Western blot， and CCK-8 was used， scratch damage assay and Transwell invasion assay to detect the proliferation， migration and invasion ability of human gastric cancer cells. Results SPTBN2 is primarily expressed in the cytoplasm. Compared with adjacent normal gastric mucosal tissues and human normal gastric epithelial cells， SPTBN2 protein is highly expressed in human gastric cancer tissues and cells (P<0.05). After downregulation of SPTBN2 in human gastric cancer cells， the contents of ferroptosis markers MDA and ROS significantly increased (P<0.01)， the content of Nrf2 protein significantly decreased (P<0.05)， and the proliferation， invasion， and migration abilities of human gastric cancer cells significantly decreased (P<0.01). Conclusion Down-regulation of SPTBN2 could induce ferroptosis in human gastric cancer cells and inhibit the proliferation， migration and invasion ability of human gastric cancer cells， and it might induce ferroptosis in human gastric cancer cells through down-regulation of Nrf2 protein.
[1] Röcken C. Predictive biomarkers in gastric cancer[J]. J Cancer Res Clin Oncol， 2023， 149(1): 467-81. doi:10.1007/s00432-022-04408-0.
[2] Smyth E C， Nilsson M， Grabsch H I， et al. Gastric cancer[J]. Lancet， 2020， 396(10251): 635-48. doi:10.1016/S0140-6736(20)31288-5.
[3] Conrad M， Kagan V E， Bayir H， et al. Regulation of lipid peroxidation and ferroptosis in diverse species[J]. Genes Dev， 2018， 32(9-10): 602-19. doi:10.1101/gad.314674.118.
[4] Norwood D A， Montalvan-Sanchez E， Dominguez R L， et al. Gastric cancer: emerging trends in prevention， diagnosis， and treatment[J]. Gastroenterol Clin North Am， 2022， 51(3): 501-18. doi:10.1016/j.gtc.2022.05.001.
[5] Tonelli C， Chio I I C， Tuveson D A. Transcriptional regulation by Nrf2[J]. Antioxid Redox Signal， 2018， 29(17): 1727-45. doi:10.1089/ars.2017.7342.
[6] Jackson M， Song W， Liu M Y， et al. Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins[J]. Nature， 2001， 410(6824): 89-93. doi:10.1038/35065091.
[7] 张 蕾， 郭亚丽， 张智辉. 下调SPTBN2通过抑制Nrf2/GPX4信号诱导肺腺癌细胞A549铁死亡[J]. 医药论坛杂志， 2023(2): 18-22.
[8] Wu C， Dong B， Huang L， et al. SPTBN2， a new biomarker of lung adenocarcinoma[J]. Front Oncol， 2021， 11: 754290. doi:10.3389/fonc.2021.754290.
[9] Wang P， Liu T， Zhao Z， et al. SPTBN2 regulated by miR-424-5p promotes endometrial cancer progression via CLDN4/PI3K/AKT axis[J]. Cell Death Discov， 2021， 7(1): 382. doi:10.1038/s41420-021-00776-7.
[10] Zeng F， Nijiati S， Tang L， et al. Ferroptosis detection: from approaches to applications[J]. Angew Chem Int Ed， 2023， 62(35): e202300379. doi:10.1002/anie.202300379.
[11] Hangauer M J， Viswanathan V S， Ryan M J， et al. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition[J]. Nature， 2017， 551(7679): 247-50. doi:10.1038/nature24297.
[12] Romaniello R， Citterio A， Panzeri E， et al. Novel SPTBN2 gene mutation and first intragenic deletion in early onset spinocerebellar Ataxia type 5[J]. Ann Clin Transl Neurol， 2021， 8(4): 956-63. doi:10.1002/acn3.51345.
[13] Dong L， Li Y， Xue D， et al. PCMT1 is an unfavorable predictor and functions as an oncogene in bladder cancer[J]. IUBMB Life， 2018， 70(4): 291-9. doi:10.1002/iub.1717.
[14] Zhou X， Lin L， Qi Y， et al. SPTBN2 promotes the progression of thyroid cancer by accelerating G1/S transition and inhibiting apoptosis[J]. Dis Markers， 2022， 2022: 2562595. doi:10.1155/2022/2562595.
[15] Chang H， Chen H， Ma T， et al. Multi-omics pan-cancer study of SPTBN2 and its value as a potential therapeutic target in pancreatic cancer[J]. Sci Rep， 2024， 14: 9764. doi:10.1038/s41598-024-60780-6.
[16] Lin L， Wu Q， Lu F， et al. Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers[J]. Front Oncol， 2023， 13: 1184079. doi:10.3389/fonc.2023.1184079.
[17] Sajadimajd S， Khazaei M. Oxidative stress and cancer: the role of Nrf2[J]. Curr Cancer Drug Targets， 2018， 18(6): 538-57. doi:10.2174/1568009617666171002144228.
[18] Hassannia B， Wiernicki B， Ingold I， et al. Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma[J]. J Clin Investig， 2018， 128(8): 3341-55. doi:10.1172/jci99032.
[19] Deng J， Lin X， Qin J， et al. SPTBN2 suppresses ferroptosis in NSCLC cells by facilitating SLC7A11 membrane trafficking and localization[J]. Redox Biol， 2024， 70: 103039. doi:10.1016/j.redox.2024.103039.
基本信息:
中图分类号:R735.2
引用信息:
[1]孟琳,那日苏,马秀梅,等.下调SPTBN2对人胃癌细胞铁死亡的诱导及生物学行为的影响[J].安徽医科大学学报().
基金信息:
内蒙古自治区自然科学基金项目（编号：2018MS08021）
2026-09-10
2026-09-10
2026-09-10