Benzo[a]pyrene promotes gastric cancer cell proliferation and metastasis likely through the Aryl hydrocarbon receptor and ERK-dependent induction of MMP9 and c-myc

Wei,Yucai; Zhao,Lei; He,Wenting; Yang,Jingwei; Geng,Chunyu; Chen,Yusheng; Liu,Tao; Chen,Hao; Li,Yumin

doi:10.3892/ijo.2016.3674

Benzo[a]pyrene promotes gastric cancer cell proliferation and metastasis likely through the Aryl hydrocarbon receptor and ERK-dependent induction of MMP9 and c-myc

Authors:
- Yucai Wei
- Lei Zhao
- Wenting He
- Jingwei Yang
- Chunyu Geng
- Yusheng Chen
- Tao Liu
- Hao Chen
- Yumin Li
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Affiliations: The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA
Published online on: August 29, 2016 https://doi.org/10.3892/ijo.2016.3674
Pages: 2055-2063

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Abstract

Gastric cancer (GC) is the fifth most common cancer worldwide and the third leading cause of global cancer-related death. Benzo[a]pyrene (BaP), a Group Ⅰ carcinogen categorized by the IARC, is a cumulative foodborne carcinogen and ubiquitous environmental pollutant with potent carcinogenic properties. However, the function and mechanism of BaP exposure on GC progression remains unclear. We investigated the role of BaP in human GC progression to identify potential mechanism underlining its carcinogenic activity. After exposure to various concentrations of BaP, human GC cells SGC-7901 and MNK-45 showed an increased capability of proliferation, migration and invasion. Further study indicated that BaP promotes the expression of matrix metalloproteinase-9 (MMP9) and c-myc at mRNA and protein level, and activates Aryl hydrocarbon receptor (AhR) and ERK pathway. Moreover, BaP-induced overexpression of MMP9 and c-myc were attenuated by the ERK inhibitor U0126 and AhR inhibitor resveratrol, respectively. These data suggest that BaP promotes proliferation and metastasis of GC cells through upregulation of MMP9 and c-myc expression, and this was likely mediated via the AhR and ERK signaling pathway.

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