Molecular Mechanisms Of Benzo[a]pyrenepromoted Proliferation And Metastasis In Human Gastric Cancer Cells

AimsGastric cancer(GC)is the most common cancer worldwide and the third leading cause of global cancer-related death. Environmental factors play very important role in GC initiation and development. BaP is a potent carcinogen that widely exists in tobacco smoke, charcoal-grilled and fried food. Experimental evidence confirmed that BaP can leads to tumors in multiple organs and closely associate with the development of liver cancer, breast cancer and lung cancer, so it has been listed as a human Group Ⅰ carcinogen by the International Agency for Research on Cancer(IARC). Previous study showed that feeding laboratory animals with BaP can induce preneoplastic lesions and cancer in the stomach, but the specific mechanism is still unclear. Therefore, the aim of this study is to reveal the impact of BaP in human GC SGC-7901 and MNK-45 cells’ proliferation and metastasis, and identify potential cellular signal pathway. MethodsSGC-7901 and MNK-45 cells were exposed to various concentrations of BaP(i.e.,0.05, 0.1, 0.5, 1, 5 μM) and vehicle(0.1%DMSO) for 16-48 h. CCK-8 assay was used to clarify the impact of BaP on GC cell proliferation. Transwell assay was used to verify the impact of BaP on GC cell invasion and metastasis. The expression of MMP9 and c-myc as well as the activation of aryl hydrocarbon receptor(AHR) and ERK signal was clarified by RT-PCR and western blot analysis. The AHR inhibitor RSV and ERK antagonist U0126 were used to elucidate whether the AHR and ERK pathway activation linked to BaP-induced MMP9 and c-myc overexpression. ResultsThe CCK-8 assay showed an increased OD value in BaP-exposed SGC-7901 and MNK-45 cells than DMSO(P<0.05), which might indicate an enhanced capability of proliferation for BaP treated cells. Transwell migration and invasion assay showed cell numbers were significantly increased on the lower surface in BaP-exposed SGC-7901 and MNK-45 cells than DMSO(P<0.05), which indicated cell migration and invasion were enhanced by BaP treatment. RT-PCR and western blot analysis showed that the expression of MMP9 and c-myc were induced by BaP. Inaddition, BaP activates AHR and ERK pathway in SGC-7901 and MNK-45 cells, and inhibition of AHR and ERK pathway by RSV and U0126 significantly attenuated BaP-induced MMP9 and c-myc expression at the mRNA and protein level. ConclusionsOur study demonstrates that BaP promoted proliferation and metastasis of GC SGC-7901 and MNK-45 cells through upregulation of MMP9 and c-myc expression. Furthermore, BaP can activate AHR and ERK pathways, which lead to the overexpression of MMP9 and c-myc.