AIM: To investigate the effect of notch1 gene on the change of proliferation and cell cycle in human glioma U251 cell line.METHODS: The lentiviral vectors,which express notch1 shRNA or notch1 intracellular domain(NICD),were constructed and transfected into U251 cells,respectively.RT-PCR and Western blotting were applied to monitor the validity of down-regulation of notch1 expression and over-expression of NICD.MTT assay was performed to examine the cell proliferation.Flow cytometric analysis was used to detect the cell cycle.RESULTS: The lentiviral vectors,which expressed notch1 shRNA and NICD,were efficient in silencing notch1 expression and over-expression of NICD.Down-regulation of notch1 gene by RNAi inhibited the cell proliferation remarkably(P0.01),arrested cell cycle at G1 phase(P0.01) and decreased the cell number of S phase(P0.01).Over-expression of NICD enhanced the cell proliferation significantly(P0.01),promoted the cell cycle at G1 phase(P0.05) and increased the cell number of S phase(P0.01).CONCLUSION: notch1 gene,which leads to change the proliferation and cell cycle in human glioma U251 cell line,is likely to be potential molecular target for glioma in gene therapy.