Daxx Mediates The Proliferation Of Vascular Smooth Muscle Cell And The Intervention Effect Of Curcumin Nicotinate

Objective: To observe the effect of curcumin trinicotinate(CurTn)on Angiotensin?(Ang?)-induced proliferation and migration through mediating Daxx/PTEN/AKT signaling pathway in vascular smooth muscle cell(VSMC).Methods: The rat VSMC were cultured in vitro and Daxx was over-expressed by lentivirus transfection.MTT and BRDU test were applied to observe cell viability and cell proliferation,flow cytometry method was applied to observe cell cycle,scratch test was applied to observe cell migration,western blot was applied to study the expression of Daxx,PTEN and p-AKT.Results: When the VSMC was incubated with 1?mol/L Ang? for 0-24 h,the expression of Daxx protein was decreased in a time-dependent manner.Daxx expression was reduced to only 38% compared with the control cells and AT1 receptor blocker could counteract this effect.When VSMC was tranfected with the pHIV-EGFP(Vector)and pHIV-EGFP-HA-Daxx(Daxx)lentivirus particles,Daxx expression of the Daxx group cells was 12 times compared with the vector group cells and it indicated the VSMC cell line stably overexpressing Daxx gene had been successfully constructed.After Daxx was overexpressed in VSMC,the cell viability,cell proliferation rate,S phase ratio and cell migration ability of Ang?-induced were significantly lower than vector cells.Further research showed that Daxx played its suppressor role during VSMC proliferation by targeting PTEN and inhibiting the activation of AKT phosphorylation.CurTn could significantly inhibit the cell viability and migration of Ang?-induced VSMC,1?mol/L was the best concentration.Further research showed that CurTn played its suppressor role during VSMC proliferation by targeting Daxx.Conclusion:(1)Daxx inhibited Ang?-induced cell proliferation and migration in VSMC by regulating the PTEN/AKT signaling pathway.(2)CurTn inhibited Ang?-induced cell proliferation and migration in VSMC by regulating the Daxx/PTEN/AKT signaling pathways.