The TGF-β/Smad Pathway Inhibitor SB431542 Enhances The Antitumor Effect Of Radiofrequency Ablation On Bladder Cancer Cells

Abstract

Hong-qing Zhou,1,* Ming-sheng Liu,1,* Ti-bin Deng,1 Ping-bo Xie,1 Wei Wang,1 Tao Shao,1 Yao Wu,1 Peng Zhang2 1Second Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Qujing City 655000, Yunnan Province, People’s Republic of China; 2Department of Urology, State Key Laboratory of Kidney Diseases, Chinese People’s Liberation Army (PLA) General Hospital/Chinese PLA Medical Academy, Beijing 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming-sheng LiuSecond Ward of Urology, Qujing Affiliated Hospital of Kunming Medical University, Huayuan Road, Qilin District, Qujing City 655000, Yunnan Province, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] ZhangDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese People’s Liberation Army (PLA) General Hospital/Chinese PLA Medical Academy, No. 28 Fuxing Road, Haidian District, Beijing City 100853, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Despite progress achieved in bladder cancer (BC) treatment, the prognosis of patients with advanced BC (ie, metastasized from the bladder to other organs) is poor. Although mortality in cases of low-grade BC is rare, the treatment, such as a radical cystectomy, often has a serious impact on the quality of life. Thus, research is needed to identify more effective treatment strategies and this work is aiming to examine the potential application of combination of radiofrequency ablation (RFA) and SB435142, a inhibitor of transforming growth factor β (TGFβ)/Smad pathway.Methods: BC cells were transplanted into nude mice (thymusdeficiency Bal B/c) to form subcutaneous tumors. The mice with subcutaneous tumors were then treated with RFA and oral administration of SB431542, an inhibitor of TGFβ/Smad signaling pathway. The antitumor effect of RFA was measured by tumor proliferation curves and micro-positron emission computed tomography (micro-PET). The effect of SB431542 on epithelial–mesenchymal transition (EMT) related regulators in subcutaneous tumor tissues formed by BC cells were examined by quantitative real-time polymerase chain reaction (qPCR) experiments.Results: The SB431542 treatment enhanced the antitumor effect of RFA on subcutaneous growth of BCs. SB431542 also decreased EMT-related regulators in subcutaneous tumor tissues formed by BC cells in nude mice.Conclusion: SB431542 enhances the effect of RFA on BC.Keywords: bladder cancer, radiofrequency ablation, SB431542, epithelial–mesenchymal transition

Keywords

• Bladder cancer
• Radiofrequency ablation
• SB431542
• Epithelial-mesenchymal transition