Speakers

Abstract

The comorbidity between cancer and depression is well noted, with cancer patients often suffering from anxiety and depression. Escitalopram (Esc) is a superior antidepressant drug among other selective serotonin reuptake inhibitors (SSRIs) that are a standard first line treatment for anxiety and depression. However, it is unclear whether SSRIs affect cancer progression and in what manner. Serotonin was found to be involved in cancer progression, angiogenesis, and inflammation, and has been shown to correlate with balance of helper T lymphocyte (HTL) subpopulation (Th1/Th2). In this study, we employed two mouse models (C57BL/6j and athymic nude mice) for pancreatic tumors to study the HTL-mediated effect of Esc on primary tumor growth, mimicking the clinical use of SSRIs in the context of cancer. Mice underwent intra-pancreatic injection of luc2-labeled Panc02 tumor cells. Tumor growth was assessed using bioluminescent imaging (IVIS Spectrum) 7 days later, and mice were divided into two groups of similar tumor size distribution. Treatment was then initiated based on i.p.-implanted 28-day Alzet osmotic pumps, containing Esc or vehicle. Mice were monitored by IVIS every week until sacrificed, then, samples of blood, spleen and tumor tissues were collected for further analyses. Surprisingly, Esc accelerated the growth of Panc02 tumors in the C57BL/6j mouse model (n=37, p=0.024) but not in the athymic nude mouse model (n=22, p=NS). Moreover, flow cytometry analysis revealed a reduced T-lymphocyte population (p<0.01), and specifically HTL subpopulation (p<0.01) in treated BL57BL/6j spleens. Tumor RNA samples of treated BL57BL/6j mice exhibited downregulation of mRNAs expression of several cytokines regarding HTL subpopulation polarization towards Th2 and Treg, suggesting a lesser anti-tumor immunity. These findings demonstrate the deleterious effects of Esc on cancer progression, corroborate the link of HTL with anti-tumor immune response to Esc, and indicate a necessity to reconsider its clinical use in the context of cancer treatment.