Impact of evodiamine on the proliferation,migration and invasion of trophoblastic cells induced by high glucose and its mechanism
OBJECTIVE To investigate the impact of evodiamine on the proliferation,migration and invasion abilities of trophoblastic cells induced by high glucose and its potential mechanism based on advanced glycation end products(AGE)/receptor for advanced glycation end products(RAGE)signaling pathway.METHODS Human trophoblastic cells HTR-8/SVneo were divided into control group,high glucose group,evodiamine low-dose group(2 μmol/L),evodiamine high-dose group(4 μmol/L),pc-NC group(transfected with pc-NC plasmid+4 μmol/L evodiamine),and pc-RAGE group(transfected with pc-RAGE plasmid+4 μmol/L evodiamine).Cells in all groups except for the control group were cultured in a high sugar(25 mmol/L glucose)environment,and cells in all groups except for the control group and the model group were transfected with the corresponding plasmids and/or received the corresponding drug interventions.The survival rate,apoptotic rate,scratch healing rate,and invasion number,as well as the protein and mRNA expressions of AGE,RAGE,nuclear factor-κB p65(NF-κB p65),matrix metalloproteinase-2(MMP-2),and MMP-9 were examined in each group.RESULTS Compared with the control group,the cell survival rate,scratch healing rate,invasions number,and the mRNA and protein expressions of MMP-2 and MMP-9 in the high glucose group significantly decreased(P＜0.05),while the apoptotic rate,the mRNA and protein expressions of AGE and RAGE,the mRNA expression of NF-κB p65,and the phosphorylation level of NF-κB p65 protein significantly increased(P＜0.05);compared with the high glucose group,the above indexes of cells in evodiamine low-dose and high-dose groups were significantly improved,and the effect of the high-dose group was significantly better than that of the low-dose group(P＜0.05);overexpression of RAGE attenuated the ameliorative effect of evodiamine on the above indexes in high glucose-induced trophoblast cells(except for AGE mRNA and protein)(P＜0.05).CONCLUSIONS Evodiamine can promote the proliferation,migration and invasion of high glucose-induced trophoblast cells and ameliorate their functional impairment,and the above effects are associated with the inhibition of the AGE/RAGE signaling pathway.
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