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

被引:13
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
相关论文
共 40 条
  • [1] Breast Cancer Statistics: Recent Trends
    Ahmad, Aamir
    [J]. BREAST CANCER METASTASIS AND DRUG RESISTANCE: CHALLENGES AND PROGRESS, 2ND EDITION, 2019, 1152 : 1 - 7
  • [2] Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells
    Arafa, El-Shaimaa A.
    Zhu, Qianzheng
    Shah, Zubair I.
    Wani, Gulzar
    Barakat, Bassant M.
    Racoma, Ira
    El-Mandy, Mohamed A.
    Wani, Altar A.
    [J]. MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2011, 706 (1-2) : 28 - 35
  • [3] Drug Combination Studies and Their Synergy Quantification Using the Chou-Talalay Method
    Chou, Ting-Chao
    [J]. CANCER RESEARCH, 2010, 70 (02) : 440 - 446
  • [4] PARP Inhibitor PJ34 Protects Mitochondria and Induces DNA-Damage Mediated Apoptosis in Combination With Cisplatin or Temozolomide in B16F10 Melanoma Cells
    Cseh, Anna Maria
    Fabian, Zsolt
    Quintana-Cabrera, Ruben
    Szabo, Aliz
    Eros, Krisztian
    Soriano, Maria Eugenia
    Gallyas, Ferenc
    Scorrano, Luca
    Sumegi, Balazs
    [J]. FRONTIERS IN PHYSIOLOGY, 2019, 10
  • [5] Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes
    Dai, Xiaofeng
    Xiang, Liangjian
    Li, Ting
    Bai, Zhonghu
    [J]. JOURNAL OF CANCER, 2016, 7 (10): : 1281 - 1294
  • [6] Cisplatin in cancer therapy: Molecular mechanisms of action
    Dasari, Shaloam
    Tchounwou, Paul Bernard
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2014, 740 : 364 - 378
  • [7] A History of Cancer Chemotherapy
    DeVita, Vincent T., Jr.
    Chu, Edward
    [J]. CANCER RESEARCH, 2008, 68 (21) : 8643 - 8653
  • [8] Breast cancer statistics and markers
    Donepudi, Mallika Siva
    Kondapalli, Kasturi
    Amos, Seelam Jeevan
    Venkanteshan, Pavithra
    [J]. JOURNAL OF CANCER RESEARCH AND THERAPEUTICS, 2014, 10 (03) : 506 - 511
  • [9] Mitochondrial Protection by PARP Inhibition
    Gallyas, Ferenc, Jr.
    Sumegi, Balazs
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (08)
  • [10] Platinum Salts in Patients with Breast Cancer: A Focus on Predictive Factors
    Garutti, Mattia
    Pelizzari, Giacomo
    Bartoletti, Michele
    Malfatti, Matilde Clarissa
    Gerratana, Lorenzo
    Tell, Gianluca
    Puglisi, Fabio
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (14)