转录组引导的药物联合疗法抑制乳腺癌细胞增殖。
Transcriptome Guided Drug Combination Suppresses Proliferation of Breast Cancer Cells.
作者信息
Shkurnikov M Yu, Poloznikov A A, Nikulin S V, Schumacher U, Wicklein D, Stürken C, Galatenko V V, Alekseev B Ya
机构信息
P. A. Hertsen Moscow Oncology Research Center, Branch of the National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia.
BioClinicum Research Center, Moscow, Russia.
出版信息
Bull Exp Biol Med. 2019 Mar;166(5):656-660. doi: 10.1007/s10517-019-04412-4. Epub 2019 Mar 22.
One of actively developing trends in modern pharmacology is the use of the transcriptome analysis for drug repositioning. We have previously detected two molecular markers of relapses in patients with malignant breast tumors: ELOVL5 and IGFBP6. Poor prognosis is associated with low expression of these markers. Here we analyze the effects of simvastatin and a new potential proteasome inhibitor K7174 inducing expression of IGFBP6 and EVOVL5 on the proliferation of breast cancer cells MDA-MB-231 and DU4475. Compound K7174 potentiates the inhibitory effect of simvastatin on the proliferation of DU4475 cells characterized by low expression of ELOVL5-IGFBP6 pair, but not on the proliferation of MDA-MB-231 cells with high expression of these markers.
现代药理学中一个积极发展的趋势是利用转录组分析进行药物重新定位。我们之前在恶性乳腺肿瘤患者中检测到两个复发的分子标志物：ELOVL5和IGFBP6。预后不良与这些标志物的低表达有关。在此，我们分析辛伐他汀和一种新的潜在蛋白酶体抑制剂K7174诱导IGFBP6和EVOVL5表达对乳腺癌细胞MDA-MB-231和DU4475增殖的影响。化合物K7174增强了辛伐他汀对以ELOVL5-IGFBP6低表达为特征的DU4475细胞增殖的抑制作用，但对这些标志物高表达的MDA-MB-231细胞的增殖没有影响。
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