Age-dependent stimulatory effect of desipramine, and fluoxetine pretreatment on metastasis formation by B16F10 melanoma in male C57BL/6 mice

Although recent data may provide theoretical support for the preventive use of antidepressants in cancer patients, so far no study has demonstrated the clinical benefits of such strategies in the general population of cancer patients [39, 4 1]. Moreover, all association between antidepressant use and the risk of tumor promotion could neither be excluded nor established. The aim of this study was to compare the effect of desipramine (a tricyclic antidepressant, TCA) and fluoxetine (a selective serotonin reuptake inhibitor, SSRI) on tumor growth of the mouse B16F10 transplanted melanoma in "young" 6-9 month old and "aged" 18-23 month old male C57BL/6 mice. Drugs were administered daily at a dose of 10 mg/kg, ip, for two weeks and tumor cc] Is were inoculated 2 h after the last antidepressant administration. Control animals were treated with saline. Tumor growth was significantly slower in aged than in young saline-treated control animals. Pretreatment with desipramine dramatically promoted metastasis formation and increased mortality rate but inhibited primary tumor growth in young males. On the other hand, both antidepressants increased primary tumor growth in aged animals, whereas metastasis was only moderately promoted. To determine the effect of antidepressant drug pretreatment and tumor progress on some parameters of cell-mediated immunity (proliferative activity and cytokine production by splenocytes) and angiogenesis, vascular endothelial growth factor (VEGF) and metalloproteinase (MMP)-9 plasma levels were established. The prometastatic effect of desipramine in young animals was connected with an increase of VEGF and MMP-9 plasma levels.