PMID- 23125179 OWN - NLM STAT- MEDLINE DCOM- 20130613 LR - 20181202 IS - 1932-8494 (Electronic) IS - 1932-8486 (Linking) VI - 296 IP - 1 DP - 2013 Jan TI - TFPI-2 downregulates multidrug resistance protein in 5-FU-resistant human hepatocellular carcinoma BEL-7402/5-FU cells. PG - 56-63 LID - 10.1002/ar.22611 [doi] AB - Tissue factor pathway inhibitor-2 (TFPI-2) is known to induce apoptosis and to suppress tumor metastasis in several types of cancer cells. However, there is little known about its reversal effect on chemoresistant tumor cells. This study investigated the effect of TFPI-2 in 5-fluorouracil (5-FU)-resistant human hepatocellular cancer BEL-7402/5-FU cells in vitro. We constructed TFPI-2 overexpression BEL-7402/5-FU cell lines and explored resistance index (RI) of 5-FU, function of the P-glycoprotein (P-gp) efflux pump, and the mRNA and protein expression of drug resistance gene, including multidrug resistance gene (MDR1), lung-resistance protein (LRP), multidrug resistance-associated protein (MRP1), glutathione-S-transferase-pi (GST-pi), excision repair cross-complementing gene 1 (ERCC1), and p38 phosphorylation. We found that TFPI-2 improved the RI of 5-FU and inhibited P-gp function. Western blotting and real-time PCR revealed that TFPI-2 also decreased mRNA and protein expression of MDR1, LRP, MRP1, GST-pi, and ERCC1, whereas p38 phosphorylation was increased. We considered that TFPI-2 reduces 5-FU resistance in BEL-7402/5-FU cells, and the mechanism appears to involve p38-mediated downregulation of drug resistance gene expression such as MDR1, LRP, MRP1, GST-pi, and ERCC1. CI - Copyright (c) 2012 Wiley Periodicals, Inc. FAU - Lu, Fei AU - Lu F AD - Microsurgical Ward Section, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China. FAU - Hou, Yong-Qiang AU - Hou YQ FAU - Song, Ying AU - Song Y FAU - Yuan, Zheng-Jiang AU - Yuan ZJ LA - eng PT - Journal Article DEP - 20121104 PL - United States TA - Anat Rec (Hoboken) JT - Anatomical record (Hoboken, N.J. : 2007) JID - 101292775 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (DNA-Binding Proteins) RN - 0 (Glycoproteins) RN - 0 (Multidrug Resistance-Associated Proteins) RN - 0 (Serine Proteinase Inhibitors) RN - 0 (Vault Ribonucleoprotein Particles) RN - 0 (major vault protein) RN - 0 (tissue-factor-pathway inhibitor 2) RN - EC 3.1.- (ERCC1 protein, human) RN - EC 3.1.- (Endonucleases) RN - U3P01618RT (Fluorouracil) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/*metabolism MH - Antimetabolites, Antineoplastic/pharmacology/therapeutic use MH - Apoptosis/drug effects MH - Carcinoma, Hepatocellular/*drug therapy/metabolism/pathology MH - Cell Line, Tumor MH - DNA-Binding Proteins/genetics/metabolism MH - Down-Regulation/*drug effects MH - *Drug Resistance, Neoplasm MH - Endonucleases/genetics/metabolism MH - Fluorouracil/pharmacology/*therapeutic use MH - Gene Expression Regulation, Neoplastic/drug effects MH - Glycoproteins/*pharmacology MH - Humans MH - In Vitro Techniques MH - Liver Neoplasms/*drug therapy/metabolism/pathology MH - Multidrug Resistance-Associated Proteins/genetics/metabolism MH - Serine Proteinase Inhibitors/pharmacology MH - Vault Ribonucleoprotein Particles/genetics/metabolism EDAT- 2012/11/06 06:00 MHDA- 2013/06/14 06:00 CRDT- 2012/11/06 06:00 PHST- 2012/05/21 00:00 [received] PHST- 2012/08/22 00:00 [accepted] PHST- 2012/11/06 06:00 [entrez] PHST- 2012/11/06 06:00 [pubmed] PHST- 2013/06/14 06:00 [medline] AID - 10.1002/ar.22611 [doi] PST - ppublish SO - Anat Rec (Hoboken). 2013 Jan;296(1):56-63. doi: 10.1002/ar.22611. Epub 2012 Nov 4.