利用掺铁纳米颗粒研究胰腺癌细胞的铁依赖性

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2023-10-30 DOI:10.1016/j.nano.2023.102714
Thanpisit Lomphithak M.Sc. , Apiwit Sae-Fung M.Sc. , Simone Sprio Ph.D. , Anna Tampieri Ph.D. , Siriporn Jitkaew Ph.D. , Bengt Fadeel M.D., Ph.D.
{"title":"利用掺铁纳米颗粒研究胰腺癌细胞的铁依赖性","authors":"Thanpisit Lomphithak M.Sc. ,&nbsp;Apiwit Sae-Fung M.Sc. ,&nbsp;Simone Sprio Ph.D. ,&nbsp;Anna Tampieri Ph.D. ,&nbsp;Siriporn Jitkaew Ph.D. ,&nbsp;Bengt Fadeel M.D., Ph.D.","doi":"10.1016/j.nano.2023.102714","DOIUrl":null,"url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor survival rates. Here, we evaluated iron-doped hydroxyapatite (FeHA) as a potential nanomedicine-based approach to combat PDAC. FeHA, in combination with a sublethal dose of the glutathione peroxidase 4 (GPX4) inhibitor RSL3, was found to trigger ferroptosis in <em>KRAS</em> mutant PANC-1 cells, but not in BxPC3 cells, while sparing normal human cells (fibroblasts and peripheral blood mononuclear cells). These findings were recapitulated in 3D spheroids generated using PDAC cells harboring wild-type <em>versus</em> mutant <em>KRAS</em>. Moreover, ferroptosis induction by FeHA plus RSL3 was reversed by the knockdown of STEAP3, a metalloreductase responsible for converting Fe<sup>3+</sup> to Fe<sup>2+</sup>. Taken together, our data show that FeHA is capable of triggering cancer cell death in a <em>KRAS</em>-selective, STEAP3-dependent manner in PDAC cells.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102714"},"PeriodicalIF":4.2000,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploiting the ferroaddiction of pancreatic cancer cells using Fe-doped nanoparticles\",\"authors\":\"Thanpisit Lomphithak M.Sc. ,&nbsp;Apiwit Sae-Fung M.Sc. ,&nbsp;Simone Sprio Ph.D. ,&nbsp;Anna Tampieri Ph.D. ,&nbsp;Siriporn Jitkaew Ph.D. ,&nbsp;Bengt Fadeel M.D., Ph.D.\",\"doi\":\"10.1016/j.nano.2023.102714\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor survival rates. Here, we evaluated iron-doped hydroxyapatite (FeHA) as a potential nanomedicine-based approach to combat PDAC. FeHA, in combination with a sublethal dose of the glutathione peroxidase 4 (GPX4) inhibitor RSL3, was found to trigger ferroptosis in <em>KRAS</em> mutant PANC-1 cells, but not in BxPC3 cells, while sparing normal human cells (fibroblasts and peripheral blood mononuclear cells). These findings were recapitulated in 3D spheroids generated using PDAC cells harboring wild-type <em>versus</em> mutant <em>KRAS</em>. Moreover, ferroptosis induction by FeHA plus RSL3 was reversed by the knockdown of STEAP3, a metalloreductase responsible for converting Fe<sup>3+</sup> to Fe<sup>2+</sup>. Taken together, our data show that FeHA is capable of triggering cancer cell death in a <em>KRAS</em>-selective, STEAP3-dependent manner in PDAC cells.</p></div>\",\"PeriodicalId\":19050,\"journal\":{\"name\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"volume\":\"55 \",\"pages\":\"Article 102714\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2023-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nanomedicine : nanotechnology, biology, and medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1549963423000655\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nanomedicine : nanotechnology, biology, and medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1549963423000655","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

胰腺导管腺癌(PDAC)是一种生存率低的毁灭性疾病。在这里,我们评估了铁掺杂羟基磷灰石(FeHA)作为一种潜在的基于纳米医学的方法来对抗PDAC。研究发现,FeHA与亚致死剂量的谷胱甘肽过氧化物酶4 (GPX4)抑制剂RSL3联合使用可触发KRAS突变体PANC-1细胞的铁凋亡,但在BxPC3细胞中没有,而正常的人类细胞(成纤维细胞和外周血单核细胞)则不受影响。这些发现在使用PDAC细胞生成的3D球体中得到了概括,这些细胞含有野生型和突变型KRAS。此外,FeHA + RSL3诱导的铁死亡可以通过敲低STEAP3(一种负责将Fe3+转化为Fe2+的金属还原酶)而逆转。综上所述,我们的数据表明FeHA能够在PDAC细胞中以kras选择性、steap3依赖性的方式触发癌细胞死亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Exploiting the ferroaddiction of pancreatic cancer cells using Fe-doped nanoparticles

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor survival rates. Here, we evaluated iron-doped hydroxyapatite (FeHA) as a potential nanomedicine-based approach to combat PDAC. FeHA, in combination with a sublethal dose of the glutathione peroxidase 4 (GPX4) inhibitor RSL3, was found to trigger ferroptosis in KRAS mutant PANC-1 cells, but not in BxPC3 cells, while sparing normal human cells (fibroblasts and peripheral blood mononuclear cells). These findings were recapitulated in 3D spheroids generated using PDAC cells harboring wild-type versus mutant KRAS. Moreover, ferroptosis induction by FeHA plus RSL3 was reversed by the knockdown of STEAP3, a metalloreductase responsible for converting Fe3+ to Fe2+. Taken together, our data show that FeHA is capable of triggering cancer cell death in a KRAS-selective, STEAP3-dependent manner in PDAC cells.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
期刊最新文献
Comparison of cholesterol transport capacity of peptide- and polymer-based lipid Nanodiscs Retraction notice to “In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies” [Nanomedicine: Nanotechnology, Biology and Medicine 10/1 (2014) 225–234] Facile fabrication of nano-bioactive glass functionalized blended hydrogel with nucleus pulposus-derived MSCs to improve regeneration potential in treatment of disc degeneration by in vivo rat model. Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a Conceptual rationale for the use of chemically modified nanocomposites for active influence on atherosclerosis using the greater omentum model of experimental animals
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1