Effect of Oxaliplatin, Olaparib and LY294002 in Combination on Triple-Negative Breast Cancer Cells

被引:17
作者
Andreidesz, Kitti [1 ]
Koszegi, Balazs [1 ]
Kovacs, Dominika [1 ]
Vantus, Viola Bagone [1 ]
Gallyas, Ferenc [1 ,2 ,3 ]
Kovacs, Krisztina [1 ]
机构
[1] Univ Pecs, Dept Biochem & Med Chem, Med Sch, H-7624 Pecs, Hungary
[2] Univ Pecs, Szentagothai Res Ctr, H-7624 Pecs, Hungary
[3] Hungarian Acad Sci, Nucl Mitochondrial Interact Res Grp, H-1052 Budapest, Hungary
关键词
olaparib; oxaliplatin; Akt pathway inhibitor; TNBC; MCF7;
D O I
10.3390/ijms22042056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Triple-negative breast cancer (TNBC) has a poor prognosis as the therapy has several limitations, most importantly, treatment resistance. In this study we examined the different responses of triple-negative breast cancer line MDA-MB-231 and hormone receptor-positive breast cancer line MCF7 to a combined treatment including olaparib, a poly-(ADP ribose) polymerase (PARP) inhibitor, oxaliplatin, a third-generation platinum compound and LY294002, an Akt pathway inhibitor. We applied the drugs in a single, therapeutically relevant concentration individually and in all possible combinations, and we assessed the viability, type of cell death, reactive oxygen species production, cell-cycle phases, colony formation and invasive growth. In agreement with the literature, the MDA-MB-231 cells were more treatment resistant than the MCF7 cells. However, and in contrast with the findings of others, we detected no synergistic effect between olaparib and oxaliplatin, and we found that the Akt pathway inhibitor augmented the cytostatic properties of the platinum compound and/or prevented the cytoprotective effects of PARP inhibition. Our results suggest that, at therapeutically relevant concentrations, the cytotoxicity of the platinum compound dominated over that of the PARP inhibitor and the PI3K inhibitor, even though a regression-based model could have indicated an overall synergy at lower and/or higher concentrations.
引用
收藏
页码:1 / 15
页数:15
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