Chen Jun-Feng, Yu Bi-Xia, Yu Rui, Ma Liang, Lv Xiu-Yi, Cheng Yue, Ma Qi
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.
Oncol Rep. 2017 Feb;37(2):721-728. doi: 10.3892/or.2017.5356. Epub 2017 Jan 5.
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.
表柔比星（EPI）是经尿道切除非肌层浸润性膀胱肿瘤（NMIBC）后最常用的膀胱内化疗药物之一，用于预防癌症复发和进展。然而，即使在膀胱肿瘤切除和膀胱内化疗后，仍有一半患者会复发和进展。RON是一种膜酪氨酸激酶受体，通常在膀胱癌细胞中过度表达，并与不良病理特征相关。本研究旨在探讨抗RON单克隆抗体Zt/g4对膀胱细胞对EPI化疗敏感性的影响。Zt/g4处理后，EPI处理的膀胱癌细胞的细胞毒性显著增加，细胞侵袭明显受到抑制。进一步研究表明，Zt/g4与EPI联合使用可促进细胞G1/S期阻滞和凋亡，这是RON信号抑制增强EPI化疗敏感性的潜在机制。因此，基于抗体的RON靶向治疗联合使用可增强膀胱内化疗的治疗效果，为进一步改善NMIBC患者的预后提供了新策略。
