[Knockdown of Grb7 inhibits growth of oral squamous cell carcinoma, cell proliferation and promoted apoptosis through ERK/FOXM1 pathway].

PURPOSE: To investigate the effect of growth factor receptor-bound 7 (Grb7) on oral squamous cell carcinoma growth and tumor xenografts.

METHODS: Cal27 and hNOK cells were cultivated, real-time PCR and Western blotting were used to detect the expression of Grb7 in hNOK and Cal27. Cal27 was transfected with Grb7 siRNA for 48 h, cell proliferation was assayed using MTT. Flow cytometry was used to determine the cell cycle and apoptosis. Western blot was used to evaluate the expression of caspase3, Bax, bcl-2, Cyclin D1, Rb, E2F1, ERK and FOXM1. Grb7 siRNA and negative control were designed and injected subcutaneously into the mice, tumor volume and weight were measured. Statistical analysis was performed using SPSS 11.0 software package.

RESULTS: Grb7 was highly expressed in Cal27 compared with hNOK. Depletion of Grb7 significantly inhibited cell proliferation, blocked G1/S phase transition, promoted cell apoptosis. Knockdown of Grb7 suppressed the expression of Cyclin D1 and Rb, upregulated E2F1 expression. Moreover, c-caspase 3 and Bax was also reduced after inhibition of Grb7. ERK/FOXM1 signaling pathway was also inhibited by Grb7. In addition, the volume and weight of tumor xenografts were reduced by siGrb7.

CONCLUSIONS: Depletion of Grb7 inhibits cell proliferation, promotes apoptosis and reduces tumor xenografts through ERK/FOXM1 pathway.