Hahne, J. C. and Honig, A. and Meyer, S. R. and Gambaryan, S. and Walter, U. and Wischhusen, J. and Haeussler, S. F. M. and Segerer, S. E. and Fujita, N. and Dietl, J. and Engel, J. B. (2012) Downregulation of AKT reverses platinum resistance of human ovarian cancers in vitro. ONCOLOGY REPORTS, 28 (6). pp. 2023-2028. ISSN 1021-335X, 1791-2431
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHASE-II TRIAL; CISPLATIN RESISTANCE; PERIFOSINE; PHOSPHORYLATION; INHIBITION; CELLS; MODULATION; CARCINOMA; PATHWAYS; PIK3CA; ovarian cancer; platinum-resistance; AKT |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Geburtshilfe) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 May 2020 05:56 |
| Last Modified: | 04 May 2020 05:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17676 |
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