TFPI-2 Downregulates Multidrug Resistance Protein in 5-FU-Resistant Human Hepatocellular Carcinoma BEL-7402/5-FU Cells

Authors

  • Fei Lu,

    1. Microsurgical Ward Section, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
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    • Fei Lu and Yong-Qiang Hou contributed equally to this work.

  • Yong-Qiang Hou,

    1. General Surgical Ward Section 3, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
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    • Fei Lu and Yong-Qiang Hou contributed equally to this work.

  • Ying Song,

    1. The Medical College of Henan University of Science and Technology, Henan, China
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  • Zheng-Jiang Yuan

    Corresponding author
    1. Microsurgical Ward Section, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
    • Microsurgical Ward Section, The First Affiliated Hospital of Henan University of Science and Technology, No. 24 Jinghua Road, Luoyang 471003, China
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Abstract

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-π (GST-π), 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-π, 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-π, and ERCC1. Anat Rec, 2013. © 2012 Wiley Periodicals, Inc.

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