Atmospheric particulate matter2.5 promotes the migration and invasion of hepatocellular carcinoma cells

Abstract

Epidemiological data has demonstrated that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 µm (PM2.5) is associated with cancer incidence. However, the precise mechanisms underlying PM2.5-mediated hepatocellular carcinoma cancer (HCC) migration and invasion remain unclear. The aim of the present study was to explore the response of the HCC cell lines HepG2 and HuH-7 to PM2.5 exposure. The results revealed that PM2.5 treatment promoted the migration and invasion of HCC cells, in addition to increasing protein levels of matrix metalloproteinase (MMP)-13. Additionally, PM2.5 induced intracellular reactive oxygen species formation in HCC cells. Further investigation revealed that phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) increased in response to PM2.5 exposure in HCC cells, and the AKT antagonist LY294002 reduced PM2.5-induced migration, invasion and MMP-13 expression. In addition, the data from the present study demonstrated that high concentrations of PM2.5 decreased the proliferation of normal HL7702 hepatocyte cells and promoted apoptosis. These results indicate that the activation of AKT by PM2.5 results in MMP-13 overexpression, and stimulates HCC cell migration and invasion. In conclusion, the results from the present study demonstrate that PM2.5 promotes HCC development and elucidate a potential underlying molecular mechanism for this effect.

Association between Ambient Particulate Matter 2.5 Exposure and Mortality in Patients with Hepatocellular Carcinoma

“…Nevertheless, the exact mechanisms of PM 2.5 -mediated HCC migration and invasion remain unclear. In a laboratory study using HCC cell lines, Zhang et al [8] revealed that PM 2.5 treatment not only stimulated the migration and invasion of HCC cells, but also increased the levels of matrix metalloproteinase (MMP)-13. Furthermore, PM 2.5 increased oxidative stress by induction of intracellular reactive oxygen species formation in HCC cells.…”

“…High concentrations of PM 2.5 decreased the proliferation of normal HL7702 hepatocyte-like cells and promoted apoptosis. Therefore, the activation of AKT by PM 2.5 resulted in MMP-13 overexpression, and stimulated HCC cell migration and invasion [8]. A previous study also indicated that the carcinogenicity of PM 2.5 might act through its collective effect on the suppression of DNA repair and augmentation of DNA replication errors [9].…”

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks

“…Multiple assays have demonstrated the effect of PM on migration and invasion pathways in cancer cells [54]. Data from specific toxicological in vitro assays and global transcriptome profiling show that cells exposed to PM 10 and PM 2.5 exhibit an increase in the activity of proteases, as well as an invasive phenotype, associated with the upregulation in metalloproteases [9,55,56]. Experiments where transepithelial electrical resistance is measured show that PM components increase cell permeability.…”

The Role of Air Pollution by the Particulate Matter in Pathogenesis of the Chronic Noninfectious Diseases

“…При долговременном действии РМ2,5 в зависимости от размера и химического состава могут возникать злокачественные новообразова-ния различной локализации [39][40][41].…”