期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms22042056
关键词
olaparib; oxaliplatin; Akt pathway inhibitor; TNBC; MCF7
资金
- European Union
- State of Hungary - European Social Fund [GINOP-2.3.2-15-2016-00049, GINOP-2.3.3-15-2016-00025, EFOP-3.6.1-16-2016-00004]
The study found that triple-negative breast cancer cells are more resistant to combined treatment compared to hormone receptor-positive breast cancer cells, and no synergistic effect was observed between olaparib and oxaliplatin, while the Akt pathway inhibitor enhanced the cytostatic properties of the platinum compound.
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.
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