The Effects Of 1,25（OH）₂D₃ On The Proliferation Of Esophageal Squamous Cell Carcinoma And Adenocarcinoma Cells

Objective: To investigate the effect of 1,25(OH)2D3 on the cell proliferation of esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC)cells and the related expression of cyclooxygenase-2(COX-2)and 5-lipoxygenase(5-LOX)metabolic pathway productions in arachidonic acid(AA)pathway,as well as the changes of vitamin D receptor(VDR),and to explore the potential anti-cancer effects and probable mechanisms of 1,25(OH)2D3 on esophageal cancer.Methods: Eca-109(ESCC)or OE-19(EAC)cells were treated with 6 different concentrations,including 100,50,10,and 1μM of 1,25(OH)2D3 for 24 and 48 h,respectively,culture medium and 0.1% DMSO were used for blank control and salute control groups.Cell proliferation was assessed by Cell Counting Kit-8 assay.Messenger RNA(m RNA)and protein expression of COX-2,5-LOX,VDR were determined by reverse transcriptase-polymerase chain reaction(RT-PCR)and Western blot,respectively.The expression of nuclear receptor VDR(n VDR)was determined by immunocytochemistry.Theconcentrationsofprostaglandin E2(PGE2)and leukotrienes B4(LTB4)were measured by ELISA Kits.Results: When compared with control group,cell growth of both Eca-109 and OE-19 cells treated by 1,25(OH)2D3 were inhibited in a time-and concentration-dependent manner,significant differences were found in cells treated under the concentration of 10,50,100μM for 24 h and 48h(p<0.05),except 10μM for 24 h in OE-19 cells(p>0.05).Time-and concentration-dependent inhibition of COX-2,5-LOX m RNA and protein expression were found both in Eca-109 and OE-19 cells treated with 1,25(OH)2D3(p<0.05),while the expression of VDR m RNA and protein showed in a time-concentration-dependent ascending manner.After 24 h and 48 h treatment with50μM 1,25(OH)2D3,the expression of n VDR in the nuclear receptor was increased both in Eca-109 and OE-19 cells,and promoted with the prolongation of intervention time(p<0.05).The PGE2 and LTB4 levels were showed a downregulation tendency both in Eca-109 and OE-19 cells(p <0.05).Conclusions: 1,25(OH)2D3 inhibited the cell growth of both Eca-109 and OE-19 cells,which may result in the upregulation of VDR,and accompanied with the inhibition of COX-2 and 5-LOX and its metabolites productions PGE2 and LTB4 expression in AA pathway.