纳米羟基磷灰石通过共同激活内质网应激和线粒体损伤来促进细胞凋亡,从而抑制胶质瘤生长

IF 5.6 1区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Yifu Wang, Hongfeng Wu, Zhu Chen, Jun Cao, Xiangdong Zhu, Xingdong Zhang
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引用次数: 0

摘要

尽管越来越多的研究表明纳米羟基磷灰石(n-HA)具有特殊的抗肿瘤作用,但其基本机制仍不清楚。内质网(ER)和线粒体是细胞内 Ca2+ 平衡的两个关键角色,两者都需要 Ca2+ 的参与。此外,内质网和线粒体之间的相互作用协调着细胞钙稳态的维持,以防止 Ca2+ 过量造成任何负面影响,因此需要深入研究 n-HA 对它们的影响。在本研究中,我们制作了针状 n-HA,从细胞和分子角度研究其抗肿瘤效果及其内在机制。体外实验数据表明,n-HA能明显减少胶质瘤细胞的生长和侵袭。值得注意的是,经n-HA处理后,ER应激生物标志物(GRP78、p-IRE1、p-PERK、PERK和ATF6)的表达均上调,促凋亡转录因子CHOP也被激活,这表明n-HA产生的ER应激引发了细胞凋亡。此外,细胞内活性氧(ROS)表达水平的升高和线粒体膜去极化以及下游细胞凋亡信号的激活,进一步证明了n-HA通过诱导线粒体损伤引起的钙离子超载具有促细胞凋亡的作用。体内数据进一步证明,n-HA 能引起细胞内 ER 应激和线粒体损伤,有效抑制胶质瘤肿瘤的生长。综上所述,n-HA共同激活细胞内ER应激和线粒体损伤是癌细胞凋亡的关键诱因,为ER-线粒体靶向抗肿瘤治疗提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to inhibit glioma growth
Despite a growing body of studies demonstrating the specific antitumor effect of nano-hydroxyapatite (n-HA), the underlying mechanism remained unclear. Endoplasmic reticulum (ER) and mitochondria are two key players in intracellular Ca2+ homeostasis and both require Ca2+ to participate. Moreover, the ER-mitochondria interplay coordinates the maintenance of cellular calcium homeostasis to prevent any negative consequences from excess of Ca2+, hence there needs in-depth study of n-HA effect on them. In this study, we fabricated needle-like n-HA to investigate the antitumor effectiveness as well as the underlying mechanisms from cellular and molecular perspectives. Data from in vitro experiments indicated that the growth and invasion of glioma cells were obviously reduced with the aid of n-HA. It's interesting to note that the expression of ER stress biomarkers (GRP78, p-IRE1, p-PERK, PERK, and ATF6) were all up-regulated after n-HA treatment, along with the activation of the pro-apoptotic transcription factor CHOP, showing that ER stress produced by n-HA triggered cell apoptosis. Moreover, the increased expression level of intracellular reactive oxygen species (ROS) and the mitochondrial membrane depolarization, as well as the downstream cell apoptotic signaling activation, further demonstrated the pro-apoptotic roles of n-HA induced Ca2+ overload through inducing mitochondria damage. The in vivo data provided additional evidence that n-HA caused ER stress and mitochondria damage in cells and effectively restrain the growth of glioma tumors. Collectively, the work showed that n-HA co-activated intracellular ER stress and mitochondria damage are critical triggers for cancer cells apoptosis, offering fresh perspectives on ER-mitochondria targeted anti-tumor therapy.
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来源期刊
Regenerative Biomaterials
Regenerative Biomaterials Materials Science-Biomaterials
CiteScore
7.90
自引率
16.40%
发文量
92
审稿时长
10 weeks
期刊介绍: Regenerative Biomaterials is an international, interdisciplinary, peer-reviewed journal publishing the latest advances in biomaterials and regenerative medicine. The journal provides a forum for the publication of original research papers, reviews, clinical case reports, and commentaries on the topics relevant to the development of advanced regenerative biomaterials concerning novel regenerative technologies and therapeutic approaches for the regeneration and repair of damaged tissues and organs. The interactions of biomaterials with cells and tissue, especially with stem cells, will be of particular focus.
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