Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis

Chen,Jun-Feng; Yu,Bi-Xia; Yu,Rui; Ma,Liang; Lv,Xiu-Yi; Cheng,Yue; Ma,Qi

doi:10.3892/or.2017.5356

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis

Authors:
- Jun-Feng Chen
- Bi-Xia Yu
- Rui Yu
- Liang Ma
- Xiu-Yi Lv
- Yue Cheng
- Qi Ma
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Affiliations: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China, Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315212, P.R. China
Published online on: January 5, 2017 https://doi.org/10.3892/or.2017.5356
Pages: 721-728
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

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