title: Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.
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.
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Chen
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
authors.forename: Bi-Xia
authors.initials: BX
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315212, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yu
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
authors.forename: Xiu-Yi
authors.initials: XY
authors.lastname: Lv
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Translational Research Laboratory for Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015251:Epirubicin / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D016196:S Phase / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D015251:Epirubicin; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases