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

[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 (As2O3) could reduce the level of S1P in humangastric cancer cell line MGC-803, indicating that As2O3 may inhibit the activity of SphK1. In this study, the effect of As2O3on the SphK1 activation pathway was investigated. Western blot and quantitative real-time PCR analysis were used toevaluate the changes in protein and mRNA levels. The multi-dimensional mass spectrometry-based shotgun lipidomicsmethod (MDMS-SL) was used for the quantitative detection of phosphatidylserine (PS) and phosphatidic acid (PA). Theresults revealed that As2O3 did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells. However,As2O3 increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS andPA in the MGC-803 cells. The outcomes suggested that As2O3 may enhance the activity of SphK1 by increasing thelevels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA. It was suggestedthat the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1.

[学科分类] 仪器

[关键词] As2O3;SphK1;PS;PA