title: Elevated prx1 provides resistance to docetaxel, but is not associated with predictive significance in lung cancer.
abstract: BACKGROUND
  This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment.
  
  
  METHODS
  Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment.
  
  
  RESULTS
  Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114).
  
  
  CONCLUSIONS
  Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.
authors.affiliation: Department of Internal Medicine, Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Korea.
authors.forename: Ki Eun
authors.initials: KE
authors.lastname: Hwang
authors.forename: Chul
authors.initials: C
authors.lastname: Park
authors.forename: Chang Hwan
authors.initials: CH
authors.lastname: Seol
authors.forename: Yu Ri
authors.initials: YR
authors.lastname: Hwang
authors.forename: June Seong
authors.initials: JS
authors.lastname: Hwang
authors.forename: Jae Wan
authors.initials: JW
authors.lastname: Jung
authors.forename: Keum Ha
authors.initials: KH
authors.lastname: Choi
authors.forename: Eun Taik
authors.initials: ET
authors.lastname: Jeong
authors.forename: Hak Ryul
authors.initials: HR
authors.lastname: Kim
keywords: Docetaxel; Lung Neoplasms; PRDX1 Protein, Human
references.citation: Oncogene. 2003 Dec 8;22(56):9075-86
references.pmid: 14663486
references.citation: Int J Cancer. 2004 Sep 10;111(4):514-21
references.pmid: 15239128
references.citation: Prostate. 2005 Oct 1;65(2):141-50
references.pmid: 15924336
references.citation: J Urol. 2011 Jun;185(6):2376-81
references.pmid: 21511293
references.citation: J Biol Chem. 1998 Oct 23;273(43):28253-60
references.pmid: 9774447
references.citation: Cancer Res. 1997 Jan 15;57(2):229-33
references.pmid: 9000560
references.citation: Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):581-91
references.pmid: 16414373
references.citation: FEBS Lett. 2005 May 23;579(13):2873-7
references.pmid: 15876430
references.citation: Cancer Res. 1996 Mar 15;56(6):1253-5
references.pmid: 8640809
references.citation: J Clin Oncol. 2005 Jan 20;23(3):422-31
references.pmid: 15659489
references.citation: Mol Cancer Ther. 2007 Feb;6(2):752-61
references.pmid: 17308071
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7421-6
references.pmid: 10377430
references.citation: IUBMB Life. 2001 Jul;52(1-2):35-41
references.pmid: 11795591
references.citation: J Mol Med (Berl). 1999 Sep;77(9):656-65
references.pmid: 10569203
references.citation: Cancer Lett. 2008 Mar 8;261(1):108-19
references.pmid: 18171600
references.citation: Clin Cancer Res. 2007 Feb 15;13(4):1308-14
references.pmid: 17317842
references.citation: Cell. 1999 Mar 19;96(6):857-68
references.pmid: 10102273
references.citation: Curr Biol. 2000 Oct 5;10(19):1201-4
references.pmid: 11050388
references.citation: Cell Biol Toxicol. 2003 Oct;19(5):285-98
references.pmid: 14703116
references.citation: Annu Rev Med. 1997;48:353-74
references.pmid: 9046968
references.citation: Mol Cell. 1998 Nov;2(5):581-91
references.pmid: 9844631
references.citation: Clin Cancer Res. 2008 Apr 15;14(8):2326-33
references.pmid: 18413821
references.citation: Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6153-60
references.pmid: 17062692
references.citation: Clin Cancer Res. 2007 Jul 1;13(13):3875-82
references.pmid: 17606720
references.citation: Anticancer Drugs. 2001 Feb;12 Suppl 1:S21-4
references.pmid: 11340900
references.citation: Mol Cell Biol. 2002 Jan;22(2):680-91
references.pmid: 11756562
references.citation: Cancer Lett. 1999 Oct 18;145(1-2):127-32
references.pmid: 10530780
references.citation: Semin Oncol. 1998 Jun;25(3 Suppl 8):5-9
references.pmid: 9704669
references.citation: Anticancer Res. 2001 May-Jun;21(3B):2085-90
references.pmid: 11497302
references.citation: J Biol Chem. 2002 Dec 6;277(49):47928-37
references.pmid: 12351634
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references.pmid: 20610543
references.citation: Cancer Res. 1998 Jan 15;58(2):241-7
references.pmid: 9443400
references.citation: Mol Cancer Res. 2009 Sep;7(9):1543-52
references.pmid: 19737972
references.citation: N Engl J Med. 2004 Oct 7;351(15):1502-12
references.pmid: 15470213
references.citation: Cancer Lett. 2000 Aug 1;156(1):27-35
references.pmid: 10840156
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713