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PM2.5 induces EMT and promotes CSC properties by activating Notch pathway in vivo and vitro.

Abstract：

:Fine particulate matter (PM2.5) has been closely linked to increased morbidity and mortality of lung cancer worldwide. However, the role of PM2.5 in the etiology of lung cancer and the mechanism involved in PM2.5 induced lung cancer are largely unknown. In this study, we performed chronic exposure animal model to investigate the carcinogenetic mechanisms of PM2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties through Notch1 signal pathway. The antagonism of Notch1 signal pathway was carried out in vitro cell lines of A549 and BEAS-2B to block EMT and CSC. We found that chronic PM2.5 exposure mice lung tissue pathology showed atypical hyperplasia of bronchiolar epithelium. Then, we discovered that chronic PM2.5 exposure induced notable EMT event and obvious CSC properties indicating the developing process of cell malignant behaviors. EMT characterized with decreased protein expression of E-cadherin and increased protein expression of Vimentin. CSC properties induced by chronic PM2.5 exposure characterized with increased cell-surface markers (ABCG2 and ALDH1A1) and self-renewal genes (SOX2 and OCT4). Furthermore, PM2.5 exposure activate Notch signal pathway by increasing expression of Notch1 and Hes1. At last, we blocked Notch signal pathway by inhibitor RO4929097 in vitro to explore the underlying mechanism mediating PM2.5 induced EMT and CSC. We found that blocking Notch1 could prevent PM2.5 induced malignant behaviors including EMT and CSC in A549 and BEAS-2B. These data revealed that the induction of EMT and CSC properties were involved in the lung cancer risk of PM2.5 in vivo, and blocking-up Notch1 may negatively regulate EMT and CSC to suppress the invasion and migration in vitro, thereby putatively serving as a novel therapeutic target for PM2.5 induced lung cancer.

journal_name

Ecotoxicol Environ Saf

journal_title

Ecotoxicology and environmental safety

authors

Wang Y,Zhong Y,Hou T,Liao J,Zhang C,Sun C,Wang G

doi

10.1016/j.ecoenv.2019.03.086

subject

Has Abstract

pub_date

2019-08-30 00:00:00

pages

159-167

eissn

0147-6513

issn

1090-2414

pii

S0147-6513(19)30358-6

journal_volume

178

pub_type

杂志文章

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PM2.5 induces EMT and promotes CSC properties by activating Notch pathway in vivo and vitro.