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APE1氧化还原抑制剂E3330可降低人乳腺癌细胞的集体细胞迁移,并在与多西他赛联合使用时减少化学侵袭和集落形成。

The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel.

作者信息

Guerreiro Patrícia S, Corvacho Eduardo, Costa João G, Saraiva Nuno, Fernandes Ana S, Castro Matilde, Miranda Joana P, Oliveira Nuno G

机构信息

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.

CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Lisbon, Portugal.

出版信息

Chem Biol Drug Des. 2017 Oct;90(4):561-571. doi: 10.1111/cbdd.12979. Epub 2017 May 3.

Abstract

The human apurinic/apyrimidinic endonuclease 1 (APE1) is an ubiquitous multifunctional DNA repair enzyme and a redox signalling protein. Our work addressed the inhibition of APE1 redox function using E3330, as single agent or in combination with docetaxel (DTX), in human breast cancer MDA-MB-231 cells. E3330 decreased the colony formation of DTX-treated cells. In addition, E3330 alone significantly reduced the collective cell migration as assessed by the wound-healing assay, whereas the combined treatment decreased chemoinvasion. These results suggest that the inhibition of APE1 redox function might have therapeutic potential by modulating cell migration and invasion in metastatic breast cancer.

摘要

人脱嘌呤/脱嘧啶核酸内切酶1(APE1)是一种普遍存在的多功能DNA修复酶和氧化还原信号蛋白。我们的研究探讨了使用E3330作为单一药物或与多西他赛(DTX)联合使用对人乳腺癌MDA-MB-231细胞中APE1氧化还原功能的抑制作用。E3330降低了DTX处理细胞的集落形成。此外,通过伤口愈合试验评估,单独使用E3330可显著降低细胞的集体迁移,而联合治疗则降低了化学侵袭。这些结果表明,抑制APE1氧化还原功能可能通过调节转移性乳腺癌细胞的迁移和侵袭而具有治疗潜力。

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