Effects of sphingosine kinase 1 inhibitors in combination with 5-FU on gastric cancer MGC-803 cells and the possible mechanisms / 西安交通大学学报(医学版)

ABSTRACT

Objective To investigate the effects of sphingosine kinase 1 (SphK1 ) inhibitor N, N-dimethylsphingosine (DMS)combined with 5-fluorouracil (5-FU)on the proliferation and apoptosis of gastric cancer MGC-803 cells and to explore the possible mechanisms involved.Methods MGC-803 cells were cultured in vitro.The effects of DMS and 5-FU on cell proliferation,apoptosis,and cell cycle distribution of MGC-803 cells were detected by MTT assay and flow cytometer (FCM),respectively.The expressions of SphK1 ,TS,DPD,NF-κB p65 and Bcl-2 proteins were detected by Western blot.Results Different concentrations of DMS or 5-FU alone or in combination could obviously inhibit the proliferation of MGC-803 cells in a dose-dependent and time-dependent manners (P0.05).As compared with the cells without drug treatment,DMS or 5-FU alone could obviously increase the apoptosis rate of MGC-803 cells (P<0.05);the apoptosis rate in the combination group was significantly higher than that in the single-drug groups (P<0.05).The expression levels of SphK1,NF-κB p65 and bcl-2 proteins were down-regulated with the treatment of DMS alone or in combination,whereas those of TS and DPD were not affected.Conclusion DMS can inhibit the proliferation and induce apoptosis of gastric cancer MGC-803 cells in vitro.It shows a good synergetic effect in combination with 5-FU,probably by down-regulating the expressions of SphK1,NF-κB p65 and Bcl-2 proteins.