SSRI use and clinical outcomes in epithelial ovarian cancer.

Abstract

Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p<0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001).Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications.

• Authors: Desiré K Christensen, Guillermo N Armaiz-Pena, Edgardo Ramirez, Koji Matsuo, Bridget Zimmerman, Behrouz Zand, Eileen Shinn, Michael J Goodheart, David Bender, Premal H Thaker, Amina Ahmed, Frank J Penedo, Koen DeGeest, Luis Mendez, Frederick Domann, Anil K Sood, Susan K Lutgendorf
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 22 Pg. 33179-91 (May 31 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27121207 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Antidepressive Agents, Second-Generation
• Ki-67 Antigen
• Receptor, Serotonin, 5-HT2A
• Serotonin Uptake Inhibitors
• Serotonin
• Sertraline

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antidepressive Agents, Second-Generation (adverse effects)
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Chi-Square Distribution
• Gene Expression Regulation, Neoplastic
• Humans
• Kaplan-Meier Estimate
• Ki-67 Antigen (metabolism)
• Mice, Nude
• Middle Aged
• Multivariate Analysis
• Neoplasm Recurrence, Local
• Neoplasms, Glandular and Epithelial (metabolism, mortality, pathology, therapy)
• Odds Ratio
• Ovarian Neoplasms (metabolism, mortality, pathology, therapy)
• Proportional Hazards Models
• Receptor, Serotonin, 5-HT2A (genetics, metabolism)
• Risk Assessment
• Risk Factors
• Serotonin (metabolism)
• Selective Serotonin Reuptake Inhibitors (adverse effects)
• Sertraline (adverse effects)
• Time Factors
• Tumor Microenvironment
• United States
• Up-Regulation
• Xenograft Model Antitumor Assays