Abstract
Objective Uterine leiomyomas (fibroids or myomas) are the most common pelvic tumor in women with about 70% lifetime incidence rate. Currently, the only definitive treatment is surgery, causing undesirable side effects and negative impact on women's quality of life, reproductive ability, and a substantial impact on healthcare costs. Therefore, curative medical treatments are needed to be developed. In this study, we investigated the impact of serotonin receptor 5-HT 1B on cell proliferation and survival in human uterine leiomyoma cells (huLM). Study design The impact of 5-HT 1B receptor on cell proliferation, survival and apoptosis was investigated using a selective 5-HTR 1B antagonist SB216641 in huLM cells, utilizing MTS, colony formation assay and Annexin V staining, respectively. Mechanisms of inhibition of cell proliferation, survival and induction of apoptosis were investigated by Western blot analysis after treatment with various doses of HT 1B antagonist. Results 5-HT 1B receptor inhibition leads to a significant decrease in proliferation and colony formation in huLM cells, reduction of cyclin D1 and alpha-smooth muscle actin (α-SMA) expressions and the activity of Mitogen Activated Protein Kinase (MAPK) ERK and Elongation Factor 2 kinase (EF2K) pathways. 5-HT 1B receptor blockage also induces apoptotic cell death by inducing cleavage of caspase-8, -9, and -3 and PARP. Conclusion Our findings show for the first time that 5-HT 1B receptor promotes uterine leiomyoma cell survival and proliferation and its inhibition may be a potential therapeutic approach for human uterine leiomyomas. Thus, 5-HT 1B expression and antagonists should be further investigated in leiomyoma tumors.
Original language | English (US) |
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Pages (from-to) | 114-119 |
Number of pages | 6 |
Journal | European Journal of Obstetrics and Gynecology and Reproductive Biology |
Volume | 206 |
DOIs | |
State | Published - Nov 1 2016 |
Externally published | Yes |
Keywords
- 5-HT
- 5-Hydroxytriptamine
- Antagonist
- Apoptosis
- Cyclin D1
- EF2K
- ERK
- Fibroid
- MAPK
- Myoma
- Proliferation
- Receptor
- SB216641
- Serotonin
- Survival
- Treatment
- Uterine leiomyoma
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology