Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1

  • Authors:
    • Oskar Hemmingsson
    • Mikael Nöjd
    • Gautam Kao
    • Peter Naredi
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/or_00000511
  • Pages: 869-875
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Abstract

Platinating agents constitute the first line treatment for ovarian cancer but treatment failure is common because of intrinsic and acquired resistance. Cancer cells develop the RASP-phenotype (cross resistance against arsenite, antimonite and platinum) associated with decreased accumulation of cisplatin and arsenite. ASNA1 is a possible subunit of a transport system for cisplatin and arsenite due to homology to arsA, an ATPase in the E. coli ars-complex responsible for efflux of arsenite and antimonite. Eukaryotic ASNA1 is a targeting factor for membrane insertion of tail-anchored proteins involved in the secretory pathway and cellular stress responses. The purpose with this study was to evaluate if ASNA1 expression influenced cisplatin, carboplatin, oxaliplatin or arsenite sensitivity in ovarian cancer. Human ovarian cancer cell line 2008 was transfected with a sense or an antisense ASNA1 construct. ASNA1 downregulated and overexpressing clones were identified by Western blots. Cell growth and chemosensitivity was determined by the MTT assay. Down-regulated ASNA1 expression was associated with retarded growth and increased sensitivity to cisplatin, carboplatin, oxaliplatin and arsenite whereas the cisplatin resistant 2008/A overexpresses ASNA1. These observations support the hypothesis that ASNA1 is a target to overcome platinum resistance in ovarian cancer.

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October 2009
Volume 22 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Hemmingsson O, Nöjd M, Kao G and Naredi P: Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1. Oncol Rep 22: 869-875, 2009
APA
Hemmingsson, O., Nöjd, M., Kao, G., & Naredi, P. (2009). Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1. Oncology Reports, 22, 869-875. https://doi.org/10.3892/or_00000511
MLA
Hemmingsson, O., Nöjd, M., Kao, G., Naredi, P."Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1". Oncology Reports 22.4 (2009): 869-875.
Chicago
Hemmingsson, O., Nöjd, M., Kao, G., Naredi, P."Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1". Oncology Reports 22, no. 4 (2009): 869-875. https://doi.org/10.3892/or_00000511