In addition, we detected the expression of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) in osteosarcoma cell treated with Eag1 small interfering RNAs (siRNAs).
In addition, selective inhibition of Eag1 significantly decreased the expression levels of cyclin D1 and E. Taken together, our data suggest that the Eag1 channel plays a crucial role in regulating the proliferation and cell cycle of osteosarcoma cells, and represents a new and effective therapeutic target for osteosarcoma.
Mechanistically, we found that overexpression of miR-34a led to decreased Eag1 expression in osteosarcoma cells while inhibition of miR-34a increased Eag1 expression.
Furthermore, treatment of an osteosarcoma xenograft model with CRAd5.TRAIL/siEag1 resulted in significant tumor regression and cancer cell apoptosis, compared with treatment with CRAd5.TRAIL or CRAd5.siEag1.
Taken together, our results suggest that Eag1 silencing inhibits tumor growth and angiogenesis in osteosarcoma via the down regulation of VEGF/PI3K/AKT signaling.
Our data provide evidence that hEAG1 is overexpressed in human osteosarcoma and the hEAG1 polyclonal antibody offers a good tool for further characterization of the oncogenic function of hEAG1 in osteosarcoma.