Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro

  • Authors:
    • J. C. Hahne
    • A. Honig
    • S. R. Meyer
    • S. Gambaryan
    • U. Walter
    • J. Wischhusen
    • S. F.M. Häussler
    • S. E. Segerer
    • N. Fujita
    • J. Dietl
    • J. B. Engel
  • View Affiliations

  • Published online on: September 18, 2012     https://doi.org/10.3892/or.2012.2041
  • Pages: 2023-2028
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Abstract

Platinum resistance is the most crucial problem for treatment of ovarian cancer. Increasing evidence points towards AKT overexpression as a mechanistic reason for this clinical condition. The present study evaluates the effect of overexpression and downregulation of AKT on the sensitivity to cisplatin in a platinum-resistant human ovarian cancer cell line and the corresponding platinum-sensitive parental cell line. A2780 and A2780cis ovarian cancer cell lines were stably transfected with an AKT-sense and AKT-antisense plasmid. Successful transfection was evaluated by western blot analysis. Cytotoxic effects of cisplatin were evaluated by metabolic (MTT) and clonogenicity assays as well as by FACS analysis. AKT overexpression (confirmed by western blotting) converted platinum-sensitive A2780 into platinum-resistant cells as shown by MTT assay. Importantly, platinum resistance of A2780cis cells could be reversed by downregulation of AKT, as demonstrated by MTT and clonogenicity assays and FACS analysis. Our data provide strong evidence that cisplatin resistance in ovarian cancer is mediated by AKT overexpression and can be overcome by AKT downregulation, thus, providing a rationale for clinical phase II/III studies combining AKT inhibitors with cisplatin.
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December 2012
Volume 28 Issue 6

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

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Spandidos Publications style
Hahne JC, Honig A, Meyer SR, Gambaryan S, Walter U, Wischhusen J, Häussler SF, Segerer SE, Fujita N, Dietl J, Dietl J, et al: Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro. Oncol Rep 28: 2023-2028, 2012
APA
Hahne, J.C., Honig, A., Meyer, S.R., Gambaryan, S., Walter, U., Wischhusen, J. ... Engel, J.B. (2012). Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro. Oncology Reports, 28, 2023-2028. https://doi.org/10.3892/or.2012.2041
MLA
Hahne, J. C., Honig, A., Meyer, S. R., Gambaryan, S., Walter, U., Wischhusen, J., Häussler, S. F., Segerer, S. E., Fujita, N., Dietl, J., Engel, J. B."Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro". Oncology Reports 28.6 (2012): 2023-2028.
Chicago
Hahne, J. C., Honig, A., Meyer, S. R., Gambaryan, S., Walter, U., Wischhusen, J., Häussler, S. F., Segerer, S. E., Fujita, N., Dietl, J., Engel, J. B."Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro". Oncology Reports 28, no. 6 (2012): 2023-2028. https://doi.org/10.3892/or.2012.2041