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

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

  • Anticancer Res. 2019 Sep;39(9):4805-4810. doi: 10.21873/anticanres.13665.
Keisuke Tamari 1,  Keisuke Sano 2 3,  Zhihao Li 2,  Yuji Seo 2,  Keisuke Otani 2,  Shotaro Tatekawa 2,  Masayasu Toratani 2,  Yuji Takaoka 2,  Yutaka Takahashi 2,  Kazumasa Minami 2,  Fumiaki Isohashi 2,  Masahiko Koizumi 3,  Kazuhiko Ogawa 2
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan tamari@radonc.med.osaka-u.ac.jp.
  • 2 Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
  • 3 Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Osaka, Japan.
PMID: 31519582 DOI: 10.21873/anticanres.13665
Abstract

Background/aim: Ro 90-7501 has been reported as an inhibitor of the amyloid β42 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.

Keywords

ATM; Ro 90-7501; cervical cancer; radiosensitizer.

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