title: Improved ataxia telangiectasia mutated kinase inhibitor KU60019 provides a promising treatment strategy for non-invasive breast cancer.
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.
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Changfei
authors.initials: C
authors.lastname: Mao
authors.affiliation: Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Science, Nanjing University of Technology, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Shuchun
authors.initials: S
authors.lastname: Li
authors.affiliation: Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.affiliation: Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Radiotherapy, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Ji
authors.affiliation: Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Changwen
authors.initials: C
authors.lastname: Jing
authors.affiliation: Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Tang
keywords: KU60019; ataxia telangiectasia mutated; chemosensitivity; doxorubicin; p-p53 (Ser15)