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

作者

Dong, TY;Peng, YP;Zhong, N;Liu, FY;Zhang, HY;Xu, MC;Liu, RT;Han, MY;Tian, XS;Jia, JH;Chang, LK;Guo, LH;Liu, SL

作者单位

[Dong, Tianyi; Peng, Yanping; Zhang, Hanyu; Jia, Jihui; Chang, Lap Kam; Liu, Shili] Shandong Univ, Sch Med, Jinan 250012, Shandong, Peoples R China.;-;[Dong, Tianyi; Tian, Xingsong] Shandong Univ, Shandong Prov Hosp, Dept Breast Thyroid Surg, Jinan 250021, Shandong, Peoples R China.;-;[Zhong, Ning; Liu, Fengyan] Shandong Univ, Dept Gastroenterol, Qilu Hosp, Jinan 250012, Shandong, Peoples R China.;-;[Xu, Mengchen; Liu, Rutao] Shandong Univ, Sch Environm Sci & Engn, Jinan 250100, Shandong, Peoples R China.;-;[Han, Mingyong] Shandong Univ, Shandong Prov Hosp, Canc Therapy & Res Ctr, Jinan 250021, Shandong, Peoples R China.;-;[Guo, Liang-Hong] Chinese Acad Sci, Res Ctr Ecoenvironm Sci, State Key Lab Environm Chem & Ecotoxicol, Beijing 100085, Peoples R China.

摘要

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/beta-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.

关键词

NORMAL-DECANOIC ACID; PHOSPHOLIPASE A(2) ENZYMES; NEW-YORK-STATE; RAT-LIVER; SECRETORY PHOSPHOLIPASE-A2; PERFLUORINATED COMPOUNDS; PEROXISOME PROLIFERATOR; PERFLUOROOCTANOIC-ACID; PERFLUOROALKYL ACIDS; PPAR-ALPHA

基本信息

所属机构:

归属医师: 田兴松韩明勇

PMID：28881615

UT：000406717200056

刊名:ONCOTARGET

年，卷(期):2017年8卷31期

页码：50911-50920

DOI：10.18632/oncotarget.17284

附件：

收录: SCIE