Abstract
The association of perfluorodecanoicacid (PFDA) with tumor promotion and associated effects is not clear. Given that PDFA is mostly consumed with food and drinking water, we evaluated the effects of PFDA on a gastric cell line. When added to cell cultures, PFDA significantly increased growth rate and colony forming ability compared with control treatment. We found that suppression of cell senescence, but not apoptosis or autophagy was associated with PFDA-induced promotion of cell amount. To determine the molecular mechanism that was involved, DNA microarray assays was used to analyze changes in gene expression in response to PFDA treatment. Data analysis demonstrated that the vascular endothelial growth factor signaling pathway had the lowest p-value, with sPLA2-IIA (pla2g2a) exhibits the most altered expression pattern within the pathway. Moreover, sPLA2-IIA and its transcription factor TCF4, known as a direct target and a binding partner of Wnt/β-catenin signaling in gastric cells respectively, were the third and second most varied genes globally. Cells transfected with expression plasmids pENTER-tcf4 and pENTER-pla2g2a show reduced cell proliferation by more than 60% and 30% respectively. Knockdown with sPLA2-IIA siRNA provided additional evidence that sPLA2-IIA was a mediator of PFDA-induced cell senescence suppression. The results suggest for the first time that PFDA induced suppression of cell senescence through inhibition of sPLA2-IIA protein expression and might increased the proliferative capacity of an existing tumor.
Highlights
Perfluorinated carboxylic acids or perfluorinated fatty acids (PFCAs) have been used for decades to make products that resist heat, oil, and water
The growth response of AGS cells varied in response to stimulation by different PFDA concentrations, this cell amount-promotion effect was verified by hepatic cell line Bel-7402 (Figure 1B) and another gastric cell line BGC823 (Supplementary Figure 1)
More evidence was obtained from colony forming assay of AGS, PFDA enhanced colony forming ability by more than 70% compared with control cells (Supplementary Figure 2), which was significantly higher than that seen with perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) or other PFCs with longer chain length at the same concentration (PFOA and PFOS, 8C; PFDA, 10C; PFUDA, 11C; PFDoA, 12C; PFTeDA, 14C) (Figure 1C)
Summary
Perfluorinated carboxylic acids or perfluorinated fatty acids (PFCAs) have been used for decades to make products that resist heat, oil, and water Because they are used in the manufacture of nonstick cookware, firefighting foam, and many other industrial products [1, 2], perfluorinated compounds can be detected globally in the environment [3, 4], wildlife [5,6,7,8] and humans [9,10,11,12,13,14,15]. Despite the evidence of PFDA toxicity, little is known of how it acts in tumor promotion
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