Improved ataxia telangiectasia mutated kinase inhibitor KU60019 provides a promising treatment strategy for non‑invasive breast cancer

Zhu,Ying; Mao,Changfei; Wu,Jianzhong; Li,Shuchun; Ma,Rong; Cao,Haixia; Ji,Minghua; Jing,Changwen; Tang,Jinhai

doi:10.3892/ol.2014.2444

Improved ataxia telangiectasia mutated kinase inhibitor KU60019 provides a promising treatment strategy for non‑invasive breast cancer

Authors:
- Ying Zhu
- Changfei Mao
- Jianzhong Wu
- Shuchun Li
- Rong Ma
- Haixia Cao
- Minghua Ji
- Changwen Jing
- Jinhai Tang
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Affiliations: Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China, Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China, School of Pharmaceutical Science, Nanjing University of Technology, Nanjing, Jiangsu 210000, P.R. China, Department of Radiotherapy, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China
Published online on: August 13, 2014 https://doi.org/10.3892/ol.2014.2444
Pages: 2043-2048

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Abstract

It has previously been reported that KU60019, as a highly effective radiosensitizer, inhibits the DNA damage response and blocks radiation‑induced phosphorylation of key ataxia telangiectasia mutated targets in human glioma cells. The present study investigated whether KU60019 affects cell physiological activities and strengthens the efficacy of doxorubicin‑induced DNA damage. It was demonstrated that the compound suppressed the proliferation of MCF‑7 cells and significantly increased chemosensitization. In addition, KU60019 (without doxorubicin) inhibited MCF‑7 cell motility and invasion, potentially by acting on the phosphorylated‑Akt and E‑cadherin signaling pathways. Although the majority of MCF‑7 cells were arrested at the G1/S phase following treatment with KU60019, the combination of the two compounds did not result in such a marked effect on the cell cycle. In conclusion, KU60019 is a potent chemosensitizer in combination with doxorubicin, therefore, it may provide a promising strategy for non‑invasive breast cancer.

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