The main molecular genetic changes identified in glioblastomas are overexpression/amplification of the epidermal growth factor receptor (EGFR) gene and mutation/ deletion of the tumor suppressor PTEN gene. These two genetic changes both play important roles in glial tumorigenesis and progression. In this study, we demonstrated that wild-type PTEN transfection inhibited the growth and transforming ability of U87MG cells by 69.3% and 73.5%, respectively. On the other hand, antisense-EGFR transfection inhibited the growth and transforming phenotype of these cells by 50.3% and 46.8%, respectively. However, cotransfection of U87MG cells with wild-type PTEN and antisense EGFR constructs could inhibit the cellular growth by 91.7%. The transforming phenotype of these cells was completely inhibited. In addition, these cotransfected cells showed a differentiated form and expressed much lower telomerase activity than cells transfected with wild-type PTEN or antisense-EGFR alone. In summary, these results suggest that cotransfection is a better approach to suppress glioma cell growth than wild-type PTEN transfer or antisense-EGFR transfection alone. This approach may prove useful as an adjunct therapy in the treatment of glioblastomas.