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.
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.
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Yucai
Y
Wei
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Lei
L
Zhao
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Wenting
W
He
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Jingwei
J
Yang
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Chunyu
C
Geng
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Yusheng
Y
Chen
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Tao
T
Liu
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Hao
H
Chen
The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Yumin
Y
Li
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D001564:Benzo(a)pyrene; D020780:Matrix Metalloproteinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D016271:Proto-Oncogene Proteins c-myc; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C489427:MYC protein, human; C535150:MAPK1 protein, human; C579270:MMP9 protein, human