Arsenic trioxide inhibits the activity of SphK1 by decreasing the level of phosphatidylserine and phosphatidic acid in the human gastric cancer cell line MGC-803  

作　　者：PEI LIU ZHE CHEN XIAOQIONG MA 

机构地区：[1]Key Laboratory of Digestive Pathophysiology of Zhejiang Province,Institute of Cancer Research,First Affiliated Hospital,Zhejiang Chinese Medical University,Hangzhou,310006,China

出　　处：《BIOCELL》2022年第3期737-743,共7页生物细胞（英文）

基　　金：This work was funded by the Natural Science Foundation of the Zhejiang Province,Grant No.LY17H280006;the National Natural Science Foundation of China,Grant No.81803776.

摘　　要：Sphingosine kinase 1(SphK1)is an important synthetase during the synthesis of sphingosine-1-phosphate(S1P)from sphingosine(Sph).Previous studies demonstrated that arsenic trioxide(As_(2)O_(3))could reduce the level of S1P in human gastric cancer cell line MGC-803,indicating that As_(2)O_(3) may inhibit the activity of SphK1.In this study,the effect of As_(2)O_(3) on the SphK1 activation pathway was investigated.Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels.The multi-dimensional mass spectrometry-based shotgun lipidomics method(MDMS-SL)was used for the quantitative detection of phosphatidylserine(PS)and phosphatidic acid(PA).The results revealed that As_(2)O_(3) did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells.However,As_(2)O_(3) increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells.The outcomes suggested that As_(2)O_(3) may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA.It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.

关 键 词：As_(2)O_(3) SphK1 PS PA 

分 类 号：R73[医药卫生—肿瘤]