title: Pro-inflammatory cytokines interleukin-1 beta, interleukin 6, and tumor necrosis factor-alpha alter the expression and function of ABCG2 in cervix and gastric cancer cells.
abstract: The ATP-binding cassette sub-family G member 2 (ABCG2) is implicated as a member of multidrug resistant proteins in tumors, mediating efflux of a wide spectrum of anticancer drugs. Pro-inflammatory cytokines, which are present within the micro-environment of tumors and inflammation, are able to modulate the expressions and activities of different drug transporters. This study was aimed to evaluate the short-term (72-h treatment) effects of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) on the expression and function of ABCG2 in cervix carcinoma and gastric cancer cells. Effects of pro-inflammatory cytokines on mRNA, protein expression, and function of ABCG2 were studied using real time RT-PCR and flow cytometry methods, respectively. HeLa cells treated with IL-1β, IL-6, or TNF-α showed decrements in ABCG2 mRNA levels without any changes in protein expression and function of ABCG2. IL-6 and TNF-α had no effects on mRNA, protein expression, and function of ABCG2 in EPG85-257 cells. Although IL-1β did not alter ABCG2 at mRNA or protein levels in EPG85-257 cells, it augmented function of ABCG2 in these cells. Mitoxantrone accumulation was also amplified in IL-1β-, IL-6- or TNF-α-treated HeLa cells and in IL-1β-treated EPG85-257 cells. In conclusion, pro-inflammatory cytokines were able to modulate the expression of ABCG2 at transcriptional and post-transcriptional levels in human cervix and gastric cancer cells.
authors.affiliation: Biotechnology Research Centers, Mashhad University of Medical Sciences, Mashhad, Iran. mosaffaf@mums.ac.ir
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mosaffa
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kalalinia
authors.forename: Herman
authors.initials: H
authors.lastname: Lage
authors.forename: Jalil Tavakol
authors.initials: JT
authors.lastname: Afshari
authors.forename: Javad
authors.initials: J
authors.lastname: Behravan
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008942:Mitoxantrone / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D008942:Mitoxantrone