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.

• Authors: Fei Wang, Xin-Jian Ruan, Hong-Yan Zhang
• Journal: Tumori (Tumori) 2015 Mar-Apr Vol. 101 Issue 2 Pg. 238-45 ISSN: 2038-2529 [Electronic] United States
• PMID: 25908029 (Publication Type: Journal Article)

Chemical References

• 2,2',4,4',5-brominated diphenyl ether
• Halogenated Diphenyl Ethers
• SNAI1 protein, human
• Snail Family Transcription Factors
• Transcription Factors
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Blotting, Western
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (metabolism, pathology)
• Epithelial-Mesenchymal Transition (drug effects)
• HCT116 Cells
• Halogenated Diphenyl Ethers (adverse effects)
• Humans
• Phenotype
• Phosphatidylinositol 3-Kinases (drug effects, metabolism)
• Proto-Oncogene Proteins c-akt (drug effects, metabolism)
• RNA Interference (drug effects)
• Real-Time Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Snail Family Transcription Factors
• Transcription Factors (drug effects, metabolism)
• Wound Healing