Hahne, Jens C. and Kurz, Antje and Meyer, Susanne R. and Dietl, Johannes and Engel, Jorg B. and Honig, Arnd (2015) Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS-126 in models of ovarian cancer. ARCHIVES OF GYNECOLOGY AND OBSTETRICS, 291 (1). pp. 131-141. ISSN 0932-0067, 1432-0711
Full text not available from this repository. (Request a copy)Abstract
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. 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. 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. 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEGATIVE BREAST-CANCER; NATURAL-KILLER-CELLS; PLATINUM RESISTANCE; IN-VITRO; CARCINOMA; AKT; INHIBITION; PATHWAYS; LINES; IMMUNOSURVEILLANCE; Ovarian cancer; AKT; Platinum-resistance; NK-cells |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2019 11:15 |
| Last Modified: | 02 Aug 2019 11:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6343 |
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