Advertisement

BDE-99 (2,2’,4,4’,5-pentabromodiphenyl ether) triggers epithelial-mesenchymal transition in colorectal cancer cells via PI3K/Akt/Snail signaling pathway

Abstract

Purpose

The gut is in direct contact with BDE-99 (2,2’,4,4’,5-pentabromodiphenyl ether), one of the most abundant PBDE congeners in the environment and in human tissues. The objective of the present study was to investigate the effects of BDE-99 on colorectal cancer (CRC) cells.

Methods

The effects of BDE-99 on cell proliferation were measured by CCK-8 assay in the CRC cell line HCT-116. Wound healing and transwell migration/invasion assays were used to test the migration and invasion of CRC cells. Factors related to epithelial-to-mesenchymal transition (EMT) were measured by real-time PCR and Western blot analysis for mRNA and protein levels, respectively.

Results

BDE-99 was found to increase migration and invasion and trigger EMT in HCT-116 cells; EMT was characterized by cells acquiring mesenchymal spindle-like morphology and by increased expression of N-cadherin with a concomitant decrease in E-cadherin. BDE-99 treatment also increased the protein and mRNA levels of the transcription factor Snail, but not Slug, Twist, and ZEB1. Knockdown of Snail by siRNA significantly attenuated BDE-99-induced EMT in HCT-116 cells, suggesting that Snail plays a crucial role in BDE-99-induced EMT. The PI3K/Akt inhibitor LY294002 completely blocked BDE-99-induced Snail and invasion of HCT-116 cells.

Conclusions

Our results revealed that BDE-99 can trigger the EMT of colon cancer cells via the PI3K/AKT/Snail signaling pathway. This study provides new insight into the tumorigenesis and metastasis of CRC stimulated by BDE-99 and possibly other PBDE congeners.

Tumori 2015; 101(2): 238 - 245

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/tj.5000229

Authors

Fei Wang, Xin-Jian Ruan, Hong-Yan Zhang

Article History

Disclosures

Financial support: No foundation supports.
Conflict of interest: The authors declare no conflict of interest.

This article is available as full text PDF.

  • If you are a Subscriber, please log in now.

  • Article price: Eur 36,00
  • You will be granted access to the article for 72 hours and you will be able to download any format (PDF or ePUB). The article will be available in your login area under "My PayPerView". You will need to register a new account (unless you already own an account with this journal), and you will be guided through our online shop. Online purchases are paid by Credit Card through PayPal.
  • If you are not a Subscriber you may:
  • Subscribe to this journal
  • Unlimited access to all our archives, 24 hour a day, every day of the week.

Authors

Affiliations

  • Medical Oncology, Beijing Military General Hospital, Beijing - China

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.