Effects of platelets-derived growth factor receptor inhibitor on radiosensitivity of glioma cells

摘要

In present study, we investigated the mechanism of AG1295, a platelets-derived growth factor receptor (PDGFR) inhibitor, on radiosensitivity of the glioma cell line SHG-44. AG1295 induced a dose dependent cytotoxicity in the glioma cell line evidenced by MTT assay and the trypan blue dye exclusion method. Sensitization to ionizing radiation of SHG-44 was observed when pretreated with AG1295. Radiosensitization reached a peak at 24h after radiation. AG1295 markedly downregulated the expression of PDGFRa, but had little effect on the expression of PDGFRp. Flow cytometer assay revealed that AG1295 increased the G1 and G2 phases of the cell cycle, and Western blotting showed decreased cyclin B1 and cyclin D1 expression. AG1295 shows radiosensitizing effects on the SHG-44 glioma cells through a mechanism involving redistribution of the cell cycle by promoting cells to enter the radiation-sensitive G1 phase and G2 phase and inhibition of sublethal damage repair.