Neurokinin-2 receptor antagonist SR48968 induced necroptosis of myeloid leukemia cells by calcium overload-driven reactive oxygen species accumulation  

作　　者：Zhibin Yan Xiangyu Hong Qihao Lin Leijie Wang Gang Shao Chentao Ge Ruilong Xia Caiyun Fu 

机构地区：[1]Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine,College of Life Sciences and Medicine,Zhejiang Sci-Tech University,Hangzhou,Zhejiang 310018,China [2]College of Life Sciences,China Jiliang University,Hangzhou,Zhejiang 310018,China

出　　处：《Genes & Diseases》2024年第5期33-35,共3页基因与疾病（英文）

基　　金：the Zhejiang Provincial Natural Science Foundation of China(No.LD22H310004);the“Pioneer”R&D program of Zhejiang,China(No.2022C03005);the National Natural Science Foundation of China(No.81770176,82204492);the Special Support Plan for Zhejiang Province High-Level Talents(China)(No.2019R52011).

摘　　要：Increasing evidence highlight tachykinin receptors as a prominent player in hematological malignancy.We previously revealed the proto-oncogenic role of neurokinin-1 receptor(NK-1R)in acute myeloid leukemia(AML),1 whereas the role of neurokinin-2 receptor(NK-2R)has not been elucidated.Herein,we found NK-2R was significantly up-regulated in AML patients in The Cancer Genome Atlas databases.This result was further confirmed in blood from AML patients and a range of human leukemia cells.Then,we verified that blocking NK-2R by SR48968 markedly promoted cell death in human myeloid leukemia without cytotoxicity to normal cells.Mechanically,we uncovered that SR48968 induced cytotoxicity through necroptosis mediated by calcium overload-driven reactive oxygen species(ROS)accumulation.In summary,our results propose that NK-2R antagonist SR48968 may be used as a new therapeutic approach for myeloid leukemia.

关 键 词：MYELOID ANTAGONIST markedly 

分 类 号：R733.7[医药卫生—肿瘤]