Controlled release of hydrogen by implantation of magnesium induces P53-mediated tumor cells apoptosis

作     者：Rui Zan Hao Wang Weijie Cai Jiahua Ni Berengere J.C.Luthringer-Feyerabend Wenhui Wang Hongzhou Peng Weiping Ji Jun Yan Jiazeng Xia Yang Song Xiaonong Zhang 

作者机构：State Key Laboratory of Metal Matrix CompositesSchool of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai200240China Institute of Metallic BiomaterialsDepartment of Biological CharacterisationHelmholtz-Zentrum Geesthacht(HZG)Geesthacht21502Germany Department of General Surgery and Translational Medicine CenterWuxi No.2 People’s HospitalAffiliated Wuxi Clinical College of Nantong UniversityJiangsu214002China Orthopaedic DepartmentShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Department of General SurgeryShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China Suzhou Origin Medical Technology Co.Ltd.Suzhou215513China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2022年第7卷第3期

页      面：385-396页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 0836[工学-生物工程] 10[医学] 

基　　金：The authors are grateful for support from the National Key Research and Development Program of China(No.2018YFC1106600) the Interdisciplinary Program of Shanghai Jiao Tong University(No.ZH2018QNB07).Thanks to Xinyue Liu(Massachusetts Institute of Technology,MIT)for suggestions for this paper 

主　　题：Biodegradable magnesium Hydrogen Tumor apoptosis Underlying mechanism P53 

摘      要：Hydrogen has been used to suppress tumor growth with considerable *** of hydrogen gas and oral ingestion of hydrogen-rich saline are two common systemic routes of hydrogen *** have developed a topical delivery method of hydrogen at targeted sites through the degradation of magnesium-based ***,the underlying mechanism of hydrogen’s role in cancer treatment remains ***,we investigate the mechanism of tumor cell apoptosis triggered by the hydrogen released from magnesium-based *** find that the localized release of hydrogen increases the expression level of P53 tumor suppressor proteins,as demonstrated by the in vitro RNA sequencing and protein expression ***,the P53 proteins disrupt the membrane potential of mitochondria,activate autophagy,suppress the reactive oxygen species in cancer cells,and finally result in tumor *** anti-tumor efficacy of magnesium-based biomaterials is further validated in vivo by inserting magnesium wire into the subcutaneous tumor in a *** also discovered that the minimal hydrogen concentration from magnesium wires to trigger substantial tumor apoptosis is 91.2μL/mm^(3)per day,which is much lower than that required for hydrogen *** together,these findings reveal the release of H2 from magnesium-based biomaterial exerts its anti-tumoral activity by activating the P53-mediated lysosome-mitochondria apoptosis signaling pathway,which strengthens the therapeutic potential of this biomaterial as localized anti-tumor treatment.