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顺铂和组蛋白去乙酰化酶抑制剂联合应用对高 Notch1 活性 MCF7 细胞的致敏作用。

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together.

机构信息

Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland.

Department of Pathophysiology, Medical University, 20-090 Lublin, Poland.

出版信息

Int J Mol Sci. 2021 May 13;22(10):5184. doi: 10.3390/ijms22105184.

DOI:10.3390/ijms22105184
PMID:34068438
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8153599/
Abstract

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug-drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.

摘要

组蛋白去乙酰化酶抑制剂 (HDIs) 是一种有前途的抗癌药物，能抑制多种类型的癌细胞增殖，包括乳腺癌 (BC) 细胞。在本研究中，我们研究了 Notch1 活性水平对顺铂 (CDDP) 与两种 HDIs（丙戊酸 (VPA) 和琥珀酰亚胺基羟肟酸 (SAHA，伏立诺他））在腔型 BC 细胞中药物相互作用的影响。通过等效应线分析确定 CDDP 和 HDIs 之间的药物相互作用类型。MCF7 细胞通过基因修饰表达不同水平的 Notch1 活性。与天然 BC 细胞相比，SAHA 或 VPA 的细胞毒性作用在 Notch1 活性降低的细胞中更高，而在 Notch1 活性增加的细胞中则更低。等效应线分析表明，CDDP 与 SAHA 或 VPA 以固定 1:1 的比例联合使用时，表现出相加或相加协同作用的相互作用。因此，用 HDIs 治疗 CDDP 可以用于优化基于 CDDP 的联合治疗，以对抗 Notch1 改变的腔型 BC。总之，HDI 和 CDDP 的联合治疗可能是 Notch1 活性改变的腔型 BC 治疗的一种有前途的治疗工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/138566e7ba73/ijms-22-05184-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/d4e755df9022/ijms-22-05184-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/21b6b73a84f8/ijms-22-05184-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/138566e7ba73/ijms-22-05184-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/d4e755df9022/ijms-22-05184-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/21b6b73a84f8/ijms-22-05184-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7c4/8153599/138566e7ba73/ijms-22-05184-g003.jpg

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