Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition

Cell Physiol Biochem. 2017;44(6):2357-2367. doi: 10.1159/000486123. Epub 2017 Dec 15.

Abstract

Background/aims: Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism.

Methods: The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes.

Results: Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells.

Conclusion: This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention.

Keywords: Benzotriazole; Endometrial carcinoma; Epithelial-mesenchymal transition; Gene microarray; Metastasis and invasion.

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Carcinogens, Environmental / adverse effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • DNA-Binding Proteins / genetics
  • Endometrial Neoplasms / chemically induced*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / pathology*
  • Endometrium / drug effects
  • Endometrium / metabolism
  • Endometrium / pathology
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Triazoles / adverse effects*

Substances

  • Carcinogens, Environmental
  • DNA-Binding Proteins
  • Triazoles
  • benzotriazole
  • Alcohol Oxidoreductases
  • C-terminal binding protein