Ro 90-7501 Is a Novel Radiosensitizer for Cervical Cancer Cells that Inhibits ATM Phosphorylation.

ABSTRACT

BACKGROUND/AIM: Ro 90-7501 has been reported as an inhibitor of the amyloid ß42 fibril assembly that is associated with Alzheimer's disease. The present study aimed to elucidate the radiosensitizing effects of Ro 90-7501 and focused on ATM signaling after irradiation. MATERIALS AND METHODS: Clonogenic survival, apoptosis, and cell-cycle assays as well as western blotting were performed in HeLa cells treated with irradiation and Ro 90-7501. Tumor growth delay assay was also performed using BALB/c-nu mice. RESULTS: The combination of irradiation with Ro 90-7501 showed significant radiosensitizing effects in clonogenic survival and tumor growth delay assays. Ro 90-7501 significantly increased apoptosis and impaired cell cycle after irradiation. Western blotting showed that Ro 90-7501 suppressed the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation. CONCLUSION: Ro 90-7501 inhibits DNA damage response by inhibiting ATM and has significant radiosensitizing effects on cervical cancer cells.