Fei Lu and Yong-Qiang Hou contributed equally to this work.
TFPI-2 Downregulates Multidrug Resistance Protein in 5-FU-Resistant Human Hepatocellular Carcinoma BEL-7402/5-FU Cells
Article first published online: 4 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
The Anatomical Record
Volume 296, Issue 1, pages 56–63, January 2013
How to Cite
Lu, F., Hou, Y.-Q., Song, Y. and Yuan, Z.-J. (2013), TFPI-2 Downregulates Multidrug Resistance Protein in 5-FU-Resistant Human Hepatocellular Carcinoma BEL-7402/5-FU Cells. Anat Rec, 296: 56–63. doi: 10.1002/ar.22611
- Issue published online: 15 DEC 2012
- Article first published online: 4 NOV 2012
- Manuscript Accepted: 22 AUG 2012
- Manuscript Received: 21 MAY 2012
- BEL-7402/5-FU cell;
- human hepatocellular carcinoma;
- multidrug resistance;
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.