Impact of fluoxetine on innate immunity and melanoma metastasis in mice

Fluoxetine, a selective serotonin reuptake inhibitor, is widely used for the treatment of depressive symptoms in cancer patients. However, there is conflicting evidence regarding its effects on immunity and cancer. The present study aimed to clarify the effect of fluoxetine administration before or after the initiation of B16F10 melanoma lung metastasis formation on cancer development.

In the present study, we used an experimental tumoral model of lung metastasis formation by melanoma B16F10 cells in C57BL/6J mice. Fluoxetine was administered 14 days before or 14 days after tumor cell injection. We assessed the mice's behavior in the forced swimming test, the formation of lung metastases, the proliferative and metabolic activity of splenocytes, and the activity of metalloproteinases.

Results showed that repeated daily fluoxetine administration (10 mg/kg) after injection of tumor cells: 1) decreased the number of metastasis in the lungs; 2) decreased immobility time in forced swimming test; 3) increased proliferative and metabolic activity of splenocytes, 4) decreased ability of splenocytes to produce metalloproteinase 9 (MMP-9) whereas fluoxetine administration before injection of tumor cells induced opposite effect.

Obtained data confirm the inhibitory effect of fluoxetine on melanoma growth, but only when this antidepressant is given to animals that already struggle with melanoma development. Fluoxetine administration before cancer development accelerates its progress and induces unbeneficial changes in immunity and metalloproteinase levels in comparison to saline-pretreated mice.