【摘要】 目的:探究前列腺六跨膜上皮抗原1（six transmembrane epithelial antigen of the prostate 1,STEAP1）在前列腺癌组织中的表达情况及STEAP1对前列腺癌22RV1和C4-2细胞系的细胞增殖、迁移和铁死亡进程的调控作用。方法:通过TIMER及UALCAN数据库检验STEAP1表达情况及临床意义；体外培养前列腺癌22RV1和C4-2细胞系并构建STEAP1敲减细胞系（siSTEAP1）和阴性对照（NC）;通过实时荧光定量PCR（quantitative real-time polymerase chain reaction, qRT-PCR）及蛋白免疫印迹（Western blot, WB）验证STEAP1敲减效率；采用集落形成实验和划痕试验检测各组细胞增殖水平及迁移情况；利用STRING数据库及数据集GSE214583探究STEAP1在前列腺癌中的潜在机制；通过检测丙二醛（malondialdehyde, MDA）水平、谷胱甘肽（glutathione, GSH）水平、亚铁离子(ferrous ion, Fe²⁺)水平以及免疫荧光检测活性氧（reactive oxygen species, ROS）水平，探讨STEAP1对铁死亡的影响；采用WB检测谷胱甘肽过氧化物酶4（glutathione peroxidase 4,GPX4）蛋白表达，并在siSTEAP1组和NC组中添加铁死亡诱导剂RSL3再通过CCK-8实验测定细胞存活率。结果:前列腺癌中STEAP1表达水平显著高于正常组织。与NC组比较，siSTEAP1组细胞增殖及迁移能力显著降低；富集分析显示STEAP1与铁死亡途径相关。siSTEAP1组MDA、Fe²⁺、ROS水平升高，GSH水平明显下降。WB结果显示，STEAP1敲减后GPX4蛋白表达下调，且细胞对RSL3的敏感性增强。结论:在人前列腺癌细胞中，抑制STEAP1能有效促进铁死亡，为靶向STEAP1联合诱导铁死亡治疗前列腺癌提供了潜在策略。更多还原

【Abstract】 Objective: To investigate the expression of six-transmembrane epithelial antigen of the prostate 1（STEAP1） in prostate cancer（PCa） tissues and its regulatory effects on proliferation, migration, and ferroptosis in PCa cell lines 22RV1 and C4-2. Methods: The expression pattern and clinical significance of STEAP1 were analyzed using TIMER and UALCAN databases. PCa 22RV1 and C4-2 cell lines were cultured in vitro, with STEAP1-knockdown（siSTEAP1） and negative control（NC） cell models established. Knockdown efficiency was verified by quantitative real-time PCR（qRT-PCR） and Western blot（WB）. Cell proliferation was assessed by colony formation assay, while migration capability was evaluated through wound healing assay. The potential mechanisms of STEAP1 in PCa were explored using STRING database and dataset GSE214583. Ferroptosis was investigated by measuring malondialdehyde（MDA）, glutathione（GSH）, ferrous ion(Fe²⁺) levels, and reactive oxygen species（ROS） via immunofluorescence. Glutathione peroxidase 4（GPX4） protein expression was detected by WB, and cell viability was examined by CCK-8 assay after treatment with ferroptosis inducer RSL3 in both siSTEAP1 and NC. Results: STEAP1 expression was significantly higher in PCa tissues than in normal tissues. Compared with NC, siSTEAP1 showed significantly inhibited proliferation and migration. Enrichment analysis revealed STEAP1 association with ferroptosis pathways. siSTEAP1 exhibited increased MDA, Fe²⁺, and ROS levels but decreased GSH levels. WB demonstrated downregulated GPX4 protein expression after STEAP1 knockdown, along with enhanced sensitivity to RSL3. Conclusion: STEAP1 inhibition promotes ferroptosis in human PCa cells, providing a potential therapeutic strategy of targeting STEAP1 combined with ferroptosis induction.更多还原