{"title":"Schizandrin A enhances the sensitivity of gastric cancer cells to 5-FU by promoting ferroptosis","authors":"","doi":"10.1007/s10616-024-00623-4","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>Schizandrin A (Sch A) exert anticancer and multidrug resistance-reversing effects in a variety of tumors, but its effect on 5-fluorouracil (5-Fu) in gastric cancer (GC) cells remains unclear. The aim of the present study was to examine the resistance-reversing effect of Schizandrin A and assess its mechanisms in 5-Fu-resistant GC cells.5-Fu-sensitive GC cells were treated with 5-Fu and 5-Fu-resistant GC cells AGS/5-Fu and SGC7901/5-Fu were were established. These cells were stimulated with Schizandrin A alone or co-treated with 5-Fu and their effect on tumor cell growth, proliferation, migration, invasion and ferroptosis-related metabolism were investigated both in vitro and in vivo. A number of additional experiments were conducted in an attempt to elucidate the molecular mechanism of increased ferroptosis. The results of our study suggest that Schizandrin A in combination with 5-Fu might be useful in treating GC by reverse drug resistance. It was shown that Schizandrin A coadministration suppressed metastasis and chemotherapy resistance in 5-Fu-resistant GC cells through facilitating the onset of ferroptosis, which is an iron-dependent form of cell death, which was further demonstrated in a xenograft nude mouse model. Mechanistically, Schizandrin A co-administration synergistically increased the expression of transferin receptor, thus iron accumulates within cells, leading to lipid peroxidation, which ultimately results in 5-Fu-resistant GC cells death. The results of this study have provided a novel strategy for increasing GC chemosensitivity, indicating Schizandrin A as a novel ferroptosis regulator. Mechanistically, ferroptosis is induced by Schizandrin A coadministration via increasing transferrin receptor expression.</p>","PeriodicalId":10890,"journal":{"name":"Cytotechnology","volume":"97 1","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotechnology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-024-00623-4","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Schizandrin A (Sch A) exert anticancer and multidrug resistance-reversing effects in a variety of tumors, but its effect on 5-fluorouracil (5-Fu) in gastric cancer (GC) cells remains unclear. The aim of the present study was to examine the resistance-reversing effect of Schizandrin A and assess its mechanisms in 5-Fu-resistant GC cells.5-Fu-sensitive GC cells were treated with 5-Fu and 5-Fu-resistant GC cells AGS/5-Fu and SGC7901/5-Fu were were established. These cells were stimulated with Schizandrin A alone or co-treated with 5-Fu and their effect on tumor cell growth, proliferation, migration, invasion and ferroptosis-related metabolism were investigated both in vitro and in vivo. A number of additional experiments were conducted in an attempt to elucidate the molecular mechanism of increased ferroptosis. The results of our study suggest that Schizandrin A in combination with 5-Fu might be useful in treating GC by reverse drug resistance. It was shown that Schizandrin A coadministration suppressed metastasis and chemotherapy resistance in 5-Fu-resistant GC cells through facilitating the onset of ferroptosis, which is an iron-dependent form of cell death, which was further demonstrated in a xenograft nude mouse model. Mechanistically, Schizandrin A co-administration synergistically increased the expression of transferin receptor, thus iron accumulates within cells, leading to lipid peroxidation, which ultimately results in 5-Fu-resistant GC cells death. The results of this study have provided a novel strategy for increasing GC chemosensitivity, indicating Schizandrin A as a novel ferroptosis regulator. Mechanistically, ferroptosis is induced by Schizandrin A coadministration via increasing transferrin receptor expression.
摘要 五味子甲素（Sch A）在多种肿瘤中具有抗癌和多药耐药性逆转作用，但其对胃癌（GC）细胞中5-氟尿嘧啶（5-Fu）的作用仍不清楚。本研究的目的是研究五味子甲素的耐药性逆转作用，并评估其在对5-Fu耐药的胃癌细胞中的作用机制。这些细胞单独或与 5-Fu 联合处理后都会受到五味子素 A 的刺激，并在体外和体内研究了它们对肿瘤细胞生长、增殖、迁移、侵袭和铁蛋白相关代谢的影响。我们还进行了其他一些实验，试图阐明铁突变增加的分子机制。我们的研究结果表明，五味子素 A 与 5-Fu 联用可能有助于通过逆转耐药性来治疗 GC。在异种移植裸鼠模型中，研究进一步证实了五味子异黄酮 A 通过促进铁素沉着（一种铁依赖性细胞死亡形式）的发生，抑制了对 5-Fu 耐药的 GC 细胞的转移和化疗耐药性。从机理上讲，同时服用五味子异黄酮 A 可协同增加转移素受体的表达，从而使铁在细胞内蓄积，导致脂质过氧化，最终导致耐 5-Fu 的 GC 细胞死亡。这项研究的结果提供了一种提高 GC 化疗敏感性的新策略，表明五味子异黄酮 A 是一种新型的铁突变调节剂。从机理上讲，五味子异黄酮 A 可通过增加转铁蛋白受体的表达来诱导铁变态反应。
期刊介绍：
The scope of the Journal includes:
1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products.
2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools.
3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research.
4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy.
5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.
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