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Archives of Gynecology and Obstetrics
Published in: Archives of Gynecology and Obstetrics 1/2015

01-01-2015 | Gynecologic Oncology

Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS-126 in models of ovarian cancer

Authors: Jens C. Hahne, Antje Kurz, Susanne R. Meyer, Johannes Dietl, Jörg B. Engel, Arnd Honig

Published in: Archives of Gynecology and Obstetrics | Issue 1/2015

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Abstract

Purpose

Platinum resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. Recently high level of AKT was shown to be involved in platinum resistance and furthermore in resistance against Natural-killer (NK)-cell mediated killing in ovarian cancer.

Methods

Here, we investigate the ability of the PI3K/AKT inhibitor AEZS-126 alone and in combination with rapamycin to selectively target ovarian cancer cell proliferation and survival in vitro by MTT-assays and FACS based analysis. Furthermore the mechanism of cytotoxicity is analysed by FACS based assays. The NK-killing efficiency of ovarian cancer cells with and without pre-treatment with AEZS-126 was analysed.

Results

AEZS-126 showed good anti-tumour activity in in vitro models of ovarian cancer. Main mechanism of cytotoxicity seems to be necroptosis which could be abrogated by co-incubation with necrostatin-1. Furthermore pre-treatment of platinum resistant cells with AEZS-126 resulted in an increased accessibility of these tumour cells for killing by NK-cells.

Conclusion

We demonstrated the highly efficient anti-tumour activity of AEZS-126 in in vitro models of ovarian cancer. Due to the good anti-tumour activity and the expected increase in NK-cell mediated killing even of platinum resistant tumour cells, AEZS-126 seems to be a promising candidate for clinical testing in ovarian cancer.
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Metadata
Title
Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS-126 in models of ovarian cancer
Authors
Jens C. Hahne
Antje Kurz
Susanne R. Meyer
Johannes Dietl
Jörg B. Engel
Arnd Honig
Publication date
01-01-2015
Publisher
Springer Berlin Heidelberg
Published in
Archives of Gynecology and Obstetrics / Issue 1/2015
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-014-3389-z

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