Anlotinib Enhances the Therapeutic Effect of Bladder Cancer with GSDMB Expression: Analyzed from TCGA Bladder Cancer Database & Mouse Bladder Cancer Cell Line

Chen Wang,1,2 Qifeng Cao,2,* Shun Zhang,2,* Hailong Liu,2 Huangqi Duan,2 Weimin Xia,2 Haibo Shen,2 Cheng Wang1 1Department of Urology, The People’s Hospital of SND, Suzhou, People’s Republic of China; 2Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Cheng Wang, Department of Urology, The People’s Hospital of SND, Suzhou, People’s Republic of China, Tel +86-15050163288, Email 15050163288@163.com Haibo Shen, Department of Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China, Tel +86-18601712802, Email shenhaibo@xinhuamed.com.cnIntroduction and Objective: The mitogen-activated protein kinase (MAPK) pathway is inhibited by the pan-target inhibitor Anlotinib, which induces tumor cell death. In addition to the common apoptosis and necrosis, there is also a pyroptosis mode of cancer cell death in recent years, which is mainly manifested by the cleavage of gasdermin proteins (GSDMs). Gasdermin B (GSDMB) participates in the progression and outcome of bladder cancer. The efficacy and mechanism of Anlotinib in the treatment of GSDMB-positive bladder tumors have not been studied to date.Methods: The relationship between GSDMB expression and tumor stage, overall survival rate, immunotherapy response, tumor recurrence and progression rate was analyzed from the TCGA bladder cancer database. Anlotinib was used to treat GSDMB-positive bladder cancer in mice followed by flow analysis of the secretion of inflammatory factors related to pyroptosis and the level of anti-tumor factors. Western blot analysis detected which MAPK and MEK signal transduction pathways.Results: TCGA data analysis showed that the overall survival rate of bladder cancer patients with high GSDMB expression was better than that of patients with low GSDMB expression. In vivo experimen