Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 49, Issue 5, Pages 2055-2063Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3674
Keywords
benzo[a]pyrene; gastric cancer; proliferation; metastasis; Aryl hydrocarbon receptor; ERK; MMP9; c-myc
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Funding
- National Natural Science Foundation of China [31270532]
- Central college basic scientific research foundation of Lanzhou university [lzujbky-2013-m04]
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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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