Journal
ONCOLOGY REPORTS
Volume 37, Issue 2, Pages 721-728Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2017.5356
Keywords
RON; non-muscle invasive bladder tumors; epirubicin; chemosensitivity; cell cycle; cell apoptosis; proliferation and invasion
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Funding
- National Natural Science Foundation of China [81272828, 31501113]
- Zhejiang Provincial Foundation for Medical and Health Sciences [2016KYB263, 2014KYB355]
- Ningbo Natural Science Foundation [2015A610224, 2015A610177]
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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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