Celecoxib Is A Preliminary Study Of Human Neuroblastoma Sh-sy-5y Cell Proliferation And The Mechanism Of Action

Objective:To investigate the influence of high selective Cyclooxygenase-2(COX-2) inhibitor celecoxib on proliferation and cell cycle of SH-SY-5Y cells and reveal the potential COX-2-dependent mechanism of celecoxib effect on SH-SY-5Y.Methods:After SH-SY-5Y cells were treated with celecoxib in different doses(10μmol/L,20μmol/L,40μmol/L,80μmol/L) with 48 hours,cellular morphology was observed via inverted microscope.Cell proliferation was measured by Methabenzthiazuron(MTT) assay in the different doses with different hours.In the meantime,cell cycle were detected via flow cytometry after incubation in different doses(10μmol/L,20μmol/L,40μmol/L,80μmol/L) with 48 hours.Western blot analysis for CyclinD1,P16,P21 was then performed before and after treatment with celecoxib in different doses(10μmol/L,20μmol/L,40μmol/L,80μmol/L) with 48 hours.Results:After SH-SY-5Y cells were treated with celecoxib in different doses (10μmol/L,20μmol/L,40μmol/L,80μmol/L) with 48 hours,the morphology of SH-SY-5Y cells changed significantly.The shape of SH-SY-5Y cells pre-treated with celecoxib was a slender,fusiform shape.SH-SY-5Y cells became short or polygon after 48 hours of treatment with different celecoxib concentrations.Celecoxib inhibited the cell proliferation in dose dependent manner.Cell cycle analysis demonstrated a dose-dependent accumulation of cells in the G₀-G₁ phase.The expression of CyclinD1,P21,P16 were detected in SH-SY-5Y cells.The expression level of CyclinD1 decreased with the increase of the dose of celecoxib, however P21,P16 increased.Conclusions:Celecoxib inhibits growth of SH-SY-5Y cells in G₁ through down-regulating the expression of CyclinD1 and up-regulating the expression of P16,P21 in vitro.The COX-2-dependent effect may exist.Celecoxib would become a promising drug as an adjuvant therapy for children with neuroblatoma.