Can the Antidepressant Fluoxetine Promote Sensitivity to Cisplatin in Bladder Cancer?

By: Jenna Carter, PhD
Posted: Monday, August 28, 2023

Studies have linked the prognosis of bladder cancer with the activation of signal transducer and activator of transcription (STAT3) and nuclear factor kappa-B (NF-κB). Fluoxetine is known to target STAT3- and NF-κB–mediated signaling, yet it is unclear whether this antidepressant has the capacity to inhibit bladder cancer. A study published in Biomedicine & Pharmacotherapy reported on the therapeutic effects of fluoxetine on bladder cancer both in vitro and in vivo. Professor Chih-Hung Chiang, of National Taiwan University Hospital, Taipei, and colleagues reported that fluoxetine may induce cytotoxicity and intrinsic/extrinsic apoptosis in bladder carcinoma and enhance the potential of cisplatin.

To examine the mechanism of action of fluoxetine, researchers focused on a cell viability assay, apoptosis assay, wound-healing assay, and invasion/migration assay. Additionally, Western blotting assays and immunofluorescence staining were used to verify its mechanisms of action. To evaluate the effects of fluoxetine in vivo, a total of 15 C57BL6/J mice (6-week-old male) were employed in this study. Mice were inoculated with MB49 murine bladder carcinoma cells, and tumor size was tracked before and after administration of either low-dose (5 mg/kg/day) or high-dose (10 mg/kg/day) fluoxetine.

Cell viability and apoptosis assays revealed that fluoxetine induced cytotoxicity and intrinsic/extrinsic apoptosis in cell lines with bladder cancer. Specifically, fluoxetine promoted both caspase-dependent and caspase-independent apoptosis signaling by activating caspase-3, 8, 9, apoptosis-inducing factor, and EndG. Fluoxetine was also found to inactivate the phosphorylation of STAT3 (Tyr705) and NF-κB (Ser536) and to suppress the nuclear translocation of NF-κB. Animal studies revealed that fluoxetine effectively delayed the progression of bladder cancer, seen by reductions in tumor weight in these mice (P < .01).

Disclosure: The study authors reported no conflicts of interest.

Biomedicine & Pharmacotherapy