Abstract B147: Lack of an additive effect of radiation treatment on PI3K or mTOR inhibition in prostate cancer cell lines

Abstract

Abstract We assessed the effect of PI3-K inhibition, mTOR inhibition and combined PI3K/mTOR inhibition in combination with ionizing radiation in prostate cancer cell lines. The treatments were studied in a cell lines with wild type PTEN status (CWR Rv1–22) and PTEN deficiency (LNCaP). Initial experiments determined concentrations of rapamycin (an mTOR antagonist) and wortmanin (a PI3-K antagonist) that resulted in an approximate 50% in cell viability at 48 hours. Cells were then treated with these agents both alone, together, or in combination with 8 gray of ionizing radiation and cell viability was assessed at 24, 48 and 72 hours. Regardless of the treatment schedule, i.e either radiation before inhibitor treatment or inhibitor treatment before radiation, we did not observe any additive effects from combination radiation and inhibitor treatment. This was regardless of whether inhibtor treatment was PI3K inhibition, mTOR inhibition, or combined treatment. Flow sorting cell cycle analysis from these studies indicates that the lack of effect might be related to the findings that radiation and PI3K/mTOR inhibition have effects of different phases of the cell cycle. This is a cell based model only and animal model data may be quite different. However, at this time PI3K/mTOR inhibition does not appear to be a mechanism for enhancing radiation sensitivity in prostate cancer. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B147.