Repurposing Ro 90-7501 as a Radiosensitizing Agent for Bladder Cancer

Abstract

Introduction: Bladder cancer ranks as the fourth most common cancer in men worldwide. While treatment often involves cystectomy, advancements in radiotherapy have made bladder preserving approaches a promising alternative, especially for improving patients' quality of life. Still, the success of radiotherapy heavily depends on how sensitive the tumor and the patient are to radiation. This makes the search for safe and effective radiosensitizing drugs for bladder cancer particularly important. Recent studies found that Ro 90-7501, a drug originally assessed for Alzheimer’s disease treatment, can enhance the radiosensitivity of cervical cancer cells. However, its effects on bladder cancer have yet to be explored. Aim: To characterize the anti-cancer potential of Ro 90-7501 on bladder cancer and normal urothelial cell lines by evaluating its radiosensitizing potential. Methods: Two human bladder cancer cell lines were used in this study: UMUC3 and UMUC5, along with one non-tumorigenic bladder epithelial cell line, SVHUC. Cells were exposed to different doses of ionizing radiation with and without Ro 90-7501. DNA double-strand break (DSB) signaling and repair were analyzed by immunofluorescence staining using anti-pATM and anti-γH2AX antibodies. The percentage of micronuclei was also assessed. The clonogenic assay was performed to evaluate the survival capacity and colony forming ability of each cell line following treatment. Results: Ro 90-7501 reduced survival in bladder cell lines. When combined with irradiation, Ro 90-7501 significantly decreased the survival of all three cell lines. γH2AX foci analysis revealed impaired DNA DSB repair kinetics in cancer cells following combination treatment, with no effect on the non-cancerous cell line. pATM activity and micronuclei percentage remained unaffected by the drug pre-treatment. Conclusion: This study revealed that the drug Ro 90-7501 is a promising radiosensitizer for bladder cancer.