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

作者：Hahne Jens C; Kurz Antje; Meyer Susanne R; Dietl Johannes; Engel Jorg B; Honig Arnd^*

来源：Archives of Gynecology and Obstetrics, 2015, 291(1): 131-141.

DOI：10.1007/s00404-014-3389-z

• Ovarian cancer
• AKT
• Platinum-resistance
• NK-cells

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.

• 出版日期2015-1