LAUSR

Bladder cancer (BC) is one of the most common malignant diseases of the urinary system, with poor prognosis and high recurrence and metastasis rate. Recent literatures suggested that BC patients have proportionately worse depression and mental health, as well as being at increased risk of suicidal death when compared to the general population, while relatively sane BC patients have a 2.2 times higher mortality rate, which means that depression can make BC worse. Imipramine is a tricyclic antidepressant, was used to treat neuropathic pain, nocturnal enuresis, and depression. Recently, imipramine has been reported to owns anti-tumor efficacy in various type of cancer. However, the effects and underlying mechanisms of imipramine on BC is remaining unclear. First, we indicated that imipramine may induce cytotoxicity of BC by MTT assay. Flow cytometry also showed that imipramine may trigger the loss of mitochondrial membrane potential, the accumulation of oxidative stress (ROS), and the activation of cleaved-caspase-3, -8 and -9. Our western blotting assay and immunofluorescence translocation staining also verified that imipramine markedly inhibited BC progression by inhibiting both EGFR/AKT/NFΚB and EGFR/ERK/NΚB signaling pathways. Furthermore, transwell and wound healing assay indicated that imipramine effectively reduced the metastatic ability of BC. In addition, the anti-tumor effect of imipramine was also validated by MB49 bearing animal model. Most importantly biochemistry level and pathology was not affected by imipramine. In conclusion, imipramine may not only suppressed BC progression by inactivation of EGFR/AKT/NFΚB and EGFR/ERK/NFΚB signaling pathways and induction of apoptosis pathways. These results suggested that imipramine has the opportunity to be a new therapeutic strategy for BC patients. Citation Format: Tsai Lin Lo, Jai-Jen Tsai, Fei-Ting Hsu, Yuan Chang. Imipramine induces apoptosis and inhibits metastasis via suppression of EGFR signaling pathway in bladder cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6154.