宫颈癌是女性的重大公共卫生问题，目前缺乏有效的治疗药物。苦参碱是传统中药苦参的成分，以其抗宫颈癌特性和诱导程序性细胞死亡的能力而闻名。诱导癌细胞铁死亡是一种新型的细胞死亡模式，未来可能成为肿瘤的有效临床治疗方法。然而，苦参碱对宫颈癌铁死亡的影响仍有待阐明。在本研究中，我们研究了苦参碱是否会诱导宫颈癌铁死亡并阐明其潜在机制。我们利用CB17严重联合免疫组化建立了SiHa来源的荷瘤小鼠模型。免疫缺陷 (SCID) 小鼠并给予一组苦参碱（25、50 和 75 mg/kg）和顺铂（2 mg/kg）。我们仔细跟踪体重和肿瘤大小的变化，并使用苏木精和伊红（H

Cervical cancer, which is a significant public health concern in women, currently lacks effective therapeutic drugs. Matrine, a constituent of the traditional Chinese herb Sophora flavescentis Radix, is known for its anti-cervical cancer properties and ability to induce programmed cell death. The induction of cancer cell ferroptosis, which is a novel cell death pattern, can become an effective clinical therapy for tumor in the future. However, the effect of matrine on ferroptosis in cervical cancer remains to be elucidated.In this study, we investigated whether matrine induces ferroptosis in cervical cancer and elucidated the underlying mechanisms.We established an SiHa-derived tumor-bearing mouse model using CB17 severe combined immunodeficient (SCID) mice and administered a group of matrine (25, 50, and 75 mg/kg) and cisplatin (2 mg/kg). We meticulously tracked alterations in body weight and tumor size and evaluated liver and kidney health using haematoxylin and eosin (H&E) staining. Using Gene Expression Omnibus (GEO) Dataset (GSE201309), we evaluated the relationship between the effects of matrine on malignant tumor cells and ferroptosis. In vitro, tetrazolium-based colorimetric (MTT), lactate dehydrogenase (LDH) and colony formation assays were used to study the effects of matrine on SiHa cell activity and cytotoxicity. We assessed ferroptosis-related protein abundance using western blotting and ferroptosis-related indices in cells using confocal immunofluorescence microscopy. The interaction of matrine with a protein linked to ferroptosis was studied using cellular thermal shift assay (CETSA). The effects of matrine on Piezo1 expression were investigated using calcium imaging. We also used Piezo1-specific siRNA to explore the role of Piezo1 in ferroptosis.Matrine administration effectively inhibited tumor growth in a SiHa-derived tumor-bearing mouse model without inducing noticeable harm. The analysis results of GEO data set show matrine-induced effects in tumor cells were indeed involved in the process of ferroptosis. Treatment with matrine resulted in a significant reduction in GPX4 protein levels and a concurrent increase in lipid peroxide and Fe2+ content, suggesting matrine-induced modulation of ferroptosis. Matrine promoted SiHa cell death in vitro, as evidenced by the results of MTT and LDH assays. Cell death coincides with increases in intracellular Fe2+, reactive oxygen species (ROS), and lipid peroxides. Our study also revealed significant upregulation of Piezo1 expression through the action of matrine, whereas transferrin receptor (Tfr) and System Xc- (xCT) expression and interaction remained unaffected. We provided further evidence that matrine induces calcium influx through the Piezo1 channel, thereby potentially influencing ferroptosis. Transfection with Piezo1 siRNA reversed the effects of matrine in SiHa cell.Our findings indicate that matrine exerts a protective effect against cervical cancer by inducing ferroptosis through the activation of Piezo1, but not xCT or Tfr.Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.