Overexpression of Insulin Receptor Substrate 1 (IRS1) Promotes Radioresistance in A172 Glioblastoma Cell Line

INTRODUCTION: Insulin receptor substrate 1 (IRS1) is the main adaptor molecule in insulin and insulin like growth factor signaling. Increased level of expression of IRS1 and IGF-1R proteins are associated with many human malignancies. They also induced resistance to therapeutic approaches such as chemo- and radiotherapy in cancer treatment but their molecular mechanisms are still unclear. Glioblastoma Multiforme (GBM) is the most common primary brain tumor in adults and radiotherapy has a pivotal role in its treatment. In this study, it is aimed to determine the relationship between IRS1 expression and radiosensitivity of GBM cells.
METHODS: Therefore, A172 cells transfected with pcDNA3.1-HA-tagged human IRS1 gene. Its overexpression was confirmed by western blot. IRS1 overexpressed A172 cells were irradiated with 5,8 and 10 Gray ionizing radiation and their effects on cell viability determined by MTT and clonogenic assay.
RESULTS: Our results showed that overexpression of IRS1 led a decrease on sensitivity of the radiation in GBM cells.
DISCUSSION AND CONCLUSION: As a conclusion, this study should be confirmed by further molecular analysis and in vivo studies. IRS1 may be a predictive marker of radiosensitivity for GBM.