Perfluorodecanoic acid (PFDA) promotes gastric cell proliferation via sPLA2-IIA

// Tianyi Dong 1, 2, * , Yanping Peng 1, * , Ning Zhong 3 , Fengyan Liu 3 , Hanyu Zhang 1 , Mengchen Xu 4 , Rutao Liu 4 , Mingyong Han 5 , Xingsong Tian 2 , Jihui Jia 1 , Lap Kam Chang 1 , Liang-Hong Guo 6 and Shili Liu 1 1 School of Medicine, Shandong University, Jinan, Shandong, 250012, China 2 Department of Breast Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, China 3 Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China 4 School of Environmental Science and Engineering, Shandong University, Jinan, Shandong, 250100, China 5 Cancer Therapy and Research Center, Shandong Provincial Hospital, Shandong university, Jinan, Shandong 250021, China 6 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China * These authors contributed equally to this work Correspondence to: Liang-Hong Guo, email: lhguo@rcees.ac.cn Shili Liu, email: liushili@sdu.edu.cn Keywords: PFDA, proliferation, sPLA2-IIA, TCF4 Received: September 06, 2016      Accepted: April 05, 2017      Published: April 20, 2017 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.