Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to inhibit glioma growth  

作　　者：Yifu Wang Hongfeng Wu Zhu Chen Jun Cao Xiangdong Zhu Xingdong Zhang 

机构地区：[1]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu 610064,P.R.China [2]College of Biomedical Engineering,Sichuan University,Chengdu 610064,P.R.China [3]Medical School,Kunming University of Science and Technology,Kunming 650500,P.R.China [4]Institute of tissue engineering and stem cells,Nanchong Central Hospital,North Sichuan Medical College,Nanchong 637000,P.R.China

出　　处：《Regenerative Biomaterials》2024年第5期121-134,共14页再生生物材料（英文版）

基　　金：supported by National Key Research and Development Program of China[grant number 2022YFC2409705];Sichuan Science and Technology Program[grant number 2023NSFSC0330];Chengdu Science and Technology Program[grant number 2021-YF08-00107-GX].

摘　　要：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 Ca^(2+)homeostasis and both require Ca^(2+)to participate.Moreover,the ER–mitochondria interplay coordinates the maintenance of cellular Ca^(2+)homeostasis to prevent any negative consequences from excess of Ca^(2+),hence there needs in-depth study of n-HA effect on them.In this study,we fabricated needle-like n-HA to investigate the anti-tumor 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 is interesting to note that the expression of ER stress biomarkers(GRP78,p-IRE1,p-PERK,PERK,and ATF6)were all upregulated 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 and the mitochondrial membrane depolarization,as well as the downstream cell apoptotic signaling activation,further demonstrated the pro-apoptotic roles of n-HA induced Ca^(2+)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.

关 键 词：NANO-HYDROXYAPATITE endoplasmic reticulum stress GLIOMA apoptosis protein mitochondria damage 

分 类 号：R739.41[医药卫生—肿瘤]