目的 基于过氧化物还原酶1（peroxiredoxin 1，PRDX1）研究粉防己碱调控磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/蛋白激酶B（protein kinase B，Akt）/糖原合成激酶-3β（glycogen synthesizing kinase-3β，GSK-3β）信号通路诱导乳腺癌细胞铁死亡的作用机制。方法 人乳腺癌MCF-7细胞转染PRDX1 siRNA后，给予粉防己碱干预，考察粉防己碱对MCF-7细胞增殖、凋亡、迁移和侵袭能力的影响；检测丙二醛（malondialdehyde，MDA）、Fe²⁺、细胞内及线粒体活性氧（reactive oxygen species，ROS）、线粒体膜电位和线粒体膜孔通透性；采用Western blotting和qRT-PCR检测电压依赖性阴离子通道1（voltage-dependent anion channel 1，VDAC1）、p53、PI3K/Akt/GSK-3β信号通路及核转录因子E2相关因子（nuclear factor E2-related factor 2，Nrf2）/血红素加氧酶-1（heme oxygenase-1，HO-1）通路相关蛋白及基因的表达。结果 粉防己碱可呈剂量相关性抑制MCF-7细胞增殖、迁移、侵袭并诱导细胞凋亡（P＜0.01），升高细胞及线粒体内ROS、MDA和Fe²⁺水平（P＜0.01），加剧脂质过氧化，降低线粒体膜电位（P＜0.01），提高线粒体膜孔通透性（P＜0.01），上调HO-1、p53、GSK-3β和VDAC1的表达（P＜0.01），下调Nrf2、PI3K、p-PI3K、Akt和p-Akt的表达（P＜0.01）。敲低PRDX1基因可显著增强粉防己碱的上述作用（P＜0.01）。结论 粉防己碱通过调控PI3K/Akt/GSK-3β信号通路诱导MCF-7细胞发生线粒体相关性铁死亡，且PRDX1在其中发挥关键的调控作用。

Objective To investigate the mechanism by which tetrandrine regulates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) signaling pathway to induce ferroptosis in breast cancer cells based on peroxiredoxin 1 (PRDX1). Methods Human breast cancer MCF-7 cells transfected with PRDX1 siRNA were treated with tetrandrine to examine its effects on cell proliferation, apoptosis, migration and invasion. The levels of malondialdehyde (MDA), Fe²⁺, intracellular and mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential, and mitochondrial membrane permeability were measured. Western blotting and qRT-PCR were used to detect the expressions of voltage-dependent anion channel 1 (VDAC1), p53, PI3K/Akt/GSK-3β signaling pathway and nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway related proteins and genes. Results Tetrandrine dose-dependently inhibited MCF-7 cell proliferation, migration and invasion while inducing apoptosis (P < 0.01), increased intracellular and mitochondrial ROS, MDA and Fe²⁺ levels (P < 0.01), aggravated lipid peroxidation, reduced mitochondrial membrane potential (P < 0.01), enhanced mitochondrial membrane permeability (P < 0.01), upregulated HO-1, p53, GSK-3β and VDAC1 expressions (P < 0.01), downregulated Nrf2, PI3K, p-PI3K, Akt and p-Akt expressions (P < 0.01). Knockdown of PRDX1 gene significantly amplified these effects of tetrandrine (P < 0.01). Conclusion Tetrandrine induces mitochondria-associated ferroptosis in MCF-7 cells via PI3K/Akt/GSK-3β signaling pathway, with PRDX1 playing a critical regulatory role.

R285.5

黑龙江省自然科学基金项目（PL2025H208）；2023年度哈尔滨商业大学镜湖学者支持计划；哈尔滨市科技计划自筹经费项目（2023ZCZJCG038）；黑龙江省中医药科研项目（ZHY2024-239）；2025年度黑龙江省省属本科高校基本科研业务费项目资助（2025-KYYWF-ZR0101）