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AACR 2022: Can an Antidepressant Suppress Progression of Muscle-Invasive Bladder Cancer?

By: Vanessa A. Carter, BS
Posted: Friday, April 15, 2022

Zhao-Lin Tan, MD, of China Medical University, Taichung City, Taiwan, and colleagues found that the antidepressant fluoxetine may effectively suppress tumor progression in patients with bladder cancer through the inactive nuclear factor-kappaB (NF-kB) signaling pathway. Additionally, the study authors suggest that the selective serotonin reuptake inhibitor may induce cytotoxicity by both extrinsic and intrinsic apoptotic pathway and inhibited metastasis ability. These preclinical study findings were presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5285).

The investigators injected mice bearing muscle-invasive bladder cancer MB49 cells in vivo with human muscle-invasive bladder cancer cells TSGH8301 and T24 cells. The study analyzed the cytotoxic, apoptotic, and metastastatic abilities of these cells after fluoxetine treatment. In an in vivo study, murine MB49 cells were subcutaneously inserted into the right flank of C57B6/J mice and treated with fluoxetine for 15 days.

The study found that fluoxetine markedly induced cytotoxicity; cleaved caspase-3, -8, and -9 expression; and inhibited migration and invasion in both TSGH8301 and T24 cells. Western blotting and reporter gene assay indicated that fluoxetine may suppress the phosphorylation and activity of NF-kB. In in vivo results, fluoxetine was shown to inhibit tumor growth and expression of NF-kB within the tumor. Results from tumor immunohistochemistry staining proved that the apoptosis markers caspase-3, -8, and -9 were all increased by fluoxetine. Aspartate transaminase and alanine transaminase values showed no significant difference in liver function between the control group and the fluoxetine treatment group. 

Disclosure: The study authors reported no conflicts of interest.


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