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.
Int J Oncol. 2016 Nov;49(5):2055-2063. doi: 10.3892/ijo.2016.3674. Epub 2016 Aug 29.
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.
胃癌（GC）是全球第五大常见癌症，也是全球癌症相关死亡的第三大主要原因。苯并[a]芘（BaP）是 IARC 归类的 1 组致癌物质，是一种累积性的食物源致癌物质和普遍存在的环境污染物，具有很强的致癌特性。然而，BaP 暴露对 GC 进展的作用和机制仍不清楚。我们研究了 BaP 在人 GC 进展中的作用，以确定其致癌活性的潜在机制。在暴露于不同浓度的 BaP 后，人 GC 细胞 SGC-7901 和 MNK-45 表现出增殖、迁移和侵袭能力的增强。进一步的研究表明，BaP 促进了基质金属蛋白酶-9（MMP9）和 c-myc 在 mRNA 和蛋白水平的表达，并激活了芳烃受体（AhR）和 ERK 通路。此外，ERK 抑制剂 U0126 和 AhR 抑制剂白藜芦醇分别减弱了 BaP 诱导的 MMP9 和 c-myc 的过表达。这些数据表明，BaP 通过上调 MMP9 和 c-myc 的表达促进 GC 细胞的增殖和转移，这可能是通过 AhR 和 ERK 信号通路介导的。
