Analysis of the in vitro effects of di-(2-ethylhexyl) phthalate exposure on human uterine leiomyoma cells

Abstract

Uterine leiomyoma is the most common benign tumor type of the female reproductive tract. Despite its high prevalence, the exact pathogenesis of the benign tumor remains unknown. In the present study, the effects of di-(2-ethylhexyl) phthalate (DEHP) on the proliferation and apoptosis rates and expression of inflammatory proteins in human leiomyoma cells were evaluated. The effects of DEHP on cell viability were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide assay. The effects on apoptosis were evaluated by western blotting, TUNEL assay and Annexin V staining. Western blotting was also performed to evaluate the expression of inflammatory proteins. It was observed that DEHP-treated leiomyoma cells had higher viability, as well as proliferating cell nuclear antigen and B-cell lymphoma 2 protein expression, and lower apoptosis rates compared with the untreated controls. Additionally, hypoxia inducible factor 1α (HIF-1α) and cyclooxygenase-2 (COX-2) expression increased in human leiomyoma cells following DEHP treatment. In conclusion, DEHP promoted cell viability and anti-apoptotic protein expression and induced HIF-1α and COX-2 expression in human leiomyoma cells. These results suggested that DEHP may disrupt mechanisms underlying various processes in human leiomyoma cells. Furthermore, the current study revealed a basic mechanism of action of DEHP in human leiomyoma cells. Further research on the effects of various endocrine disruptors on the pathogenesis of uterine leiomyoma during early development may reveal strategies to prevent this disease.