Polo-like kinase 1 inhibitor BI6727 sensitizes 9L gliosarcoma cells to ionizing irradiation

Abstract

Surgery, chemotherapy and radiotherapy remain as the major treatment strategies for cancers. Some agents such as anti-cancer drugs have capacity to enhance the radiation sensitivity of cancer cells at G2/M phase, leading to an improved radiotherapeutic efficacy. BI6727 is an ATP-competitive polo-like kinase 1 (Plk 1) inhibitor and an anti-cancer drug. Using the radio-resistant 9L rat gliosarcoma cells as model, we examined the effect of BI6727 on cell growth and assessed the chemo-radiotherapeutic efficiency between 150 kVp conventional irradiation (dose rate of 0.76 Gy min−1) and 66 keV synchrotron x-ray broad beam irradiation (dose rate of 46 Gy s−1). Our studies showed that BI6727 significantly caused cell growth arrest at G2/M phase and inhibited 9L cell proliferation with EC50 of 58.1 nM. In combinatory treatment, irradiation of BI6727-treated 9L cells with synchrotron x-rays at a dose rate of 46 Gy s−1 resulted in significant reduction of the cell survival compared to the conventional x-rays at a dose rate of 0.76 Gy min−1. These results indicated that Plk1 inhibitor BI6727 enhanced radio-sensitization of 9L cells in a dose rate dependent manner. For clinical application, irradiation with high dose rate is a promising strategy to improve chemo-radiotherapeutic efficacy for gliosarcoma cancer.