IFNγ inhibition of cell growth in glioblastomas is accompanied by induction of the cyclin dependent kinase inhibitor p21

Glioblastoma is a frequently occurring and highly aggressive form of brain cancer. It is characterized by uncontrolled cell growth caused by a loss of cell cycle regulation, frequently involving mutations in the tumor suppressor genes p53 and p16. In this study we determine the antiproliferative effects of interferon gamma (IFNγ) on the glioblastoma cell lines T98G, SNB-19, U-373, and U-118, with a focus on the induction of p21 by IFNγ. IFNγ was found to inhibit the growth of all cell lines, with percent inhibition values ranging from 82.2% to 45.4%. Flow cytometry analysis showed that IFNγ treatment caused a delay in the cell cycle generally occurring between the G1 and early S phases. The strength of this delay varied, correlating with the degree by which IFNγ inhibited proliferation of each cell line. Further experimentation showed that IFNγ treatment induced the production of the cyclin dependent kinase inhibitor (CKI) p21 in all cell lines. Cells treated with IFNγ produced significant amounts of p21, as compared to media-treated cells. Furthermore, cell lines showing greater inhibition by IFNγ also showed greater p21 production in response to IFNγ. These results show that IFNγ has significant antiproliferative effects on glioblastoma cell lines tested and suggest that p21 plays a role in mediating these effects.

Duke Scholars

Author Amy Claudine Hobeika Surgery, Surgical Sciences