顺铂（CDDP）与组蛋白去乙酰化酶抑制剂（HDIs）在 Notch1 活性改变的 MDA-MB-231 三阴性乳腺癌（TNBC）细胞中的相加药物相互作用——一种等辐射分析。
Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.
机构信息
Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland.
Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2 Street, 20-090 Lublin, Poland.
出版信息
Int J Mol Sci. 2019 Jul 26;20(15):3663. doi: 10.3390/ijms20153663.
The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro. The combination of CDDP/SAHA and CDDP/VPA in the MDA-MB-231 triple negative breast cancer (TNBC) cells with increased activity of Notch1, as well as CDDP/VPA in the MDA-MB-231 cells with decreased activity of Notch1, yielded an additive interaction, whereas additivity with a tendency towards antagonism was observed for the combination of CDDP/SAHA in MDA-MB-231 cells with the decreased activity of Notch1. Our studies demonstrated that SAHA and VPA might be considered as potential therapeutic agents in combination therapy with CDDP against TNBC with altered Notch1 activity.
本研究旨在探讨 Notch1 活性水平对顺铂（CDDP）与两种组蛋白去乙酰化酶抑制剂（HDIs）-丙戊酸（VPA）和伏立诺他（SAHA）在三阴性乳腺癌（TNBC）细胞中药物相互作用的影响。采用转染法构建 Notch1 活性增强和降低的稳定乳腺癌（BC）细胞系。通过 Notch1 活性差异的 MDA-MB-231 细胞体外增殖的等效应分析，确定 CDDP 和 HDIs 之间的相互作用类型。在 Notch1 活性增强的 MDA-MB-231 三阴性乳腺癌（TNBC）细胞中，CDDP/SAHA 和 CDDP/VPA 联合用药以及 Notch1 活性降低的 MDA-MB-231 细胞中 CDDP/VPA 联合用药均产生相加作用，而 Notch1 活性降低的 MDA-MB-231 细胞中 CDDP/SAHA 联合用药则表现出相加作用趋势的拮抗作用。本研究表明，SAHA 和 VPA 可能被认为是 Notch1 活性改变的 TNBC 与 CDDP 联合治疗的潜在治疗药物。
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