摘要
整合素受体被认为是致癌的关键因素。αIIbβ3-整合素(GP IIb/IIIa)是血小板表面的主要糖蛋白,它也存在于某些癌细胞系中。其作用于肿瘤细胞的分子机制尚不清楚。本研究提出了两个αIIbβ3-整合素:阿昔单抗和依替巴肽对细胞凋亡的影响,如在MCF-7乳腺癌细胞中对脯氨酸氧化酶(POX)的表达,信号分子ERK 1 / 2,转录因子NF-κB和HIF-1κα,血管内皮生长因子(VEGF)以及DNA的生物合成,的胶原的生物合成和脯氨酸肽酶活性等影响。配体诱导的细胞凋亡,但我们在测试不同αIIbβ3-整合素时发现其分子作用机制存在显著差异。这些差异包括POX, HIF-1α, NF-κB,VEGF的表达,血管内皮生长因子和胶原的生物合成。依替巴肽使MCF-7细胞凋亡的活性比阿昔单抗更强。这项研究的结果表明,依替巴肽可以被认为是一个新的抗癌治疗药物。
关键词: αIIbβ3-整合素,αIIbβ3-整合素,阿昔单抗,依替巴肽,MCF-7乳腺癌细胞,细胞凋亡
Current Drug Targets
Title:αIIbβ3-integrin Ligands: Abciximab and Eptifibatide as Proapoptotic Factors in MCF-7 Human Breast Cancer Cells
Volume: 16 Issue: 13
Author(s): Joanna Kononczuk, Arkadiusz Surazynski, Urszula Czyzewska, Izabela Prokop, Michal Tomczyk, Jerzy Palka and Wojciech Miltyk
Affiliation:
关键词: αIIbβ3-整合素,αIIbβ3-整合素,阿昔单抗,依替巴肽,MCF-7乳腺癌细胞,细胞凋亡
摘要: Integrin receptors are considered to be the key factors in carcinogenesis. αIIbβ3-Integrin (GP IIb/IIIa) is the main glycoprotein of the surface of platelets, its presence has also been noted on the certain cancer cell lines. The molecular mechanism of its action in cancer cells remains unknown. This study presents effects of two αIIbβ3-inhibitors: Abciximab and Eptifibatide on apoptosis, expression of proline oxidase (POX), signaling molecules ERK 1/2, transcription factor NF-κB and HIF-1α, vascular endothelial growth factor (VEGF) as well as DNA biosynthesis, collagen biosynthesis and prolidase activity in MCF-7 breast cancer cells. Both ligands induced apoptosis, however we found significant differences in molecular mechanism of action between tested αIIbβ3-inhibitors. These differences include expression of POX, HIF-1α, NF-κB,VEGF and collagen biosynthesis. Eptifibatide presented stronger proapoptotic activity in MCF-7 cells than Abciximab. Results of this study suggest that Eptifibatide may be considered as a novel candidate for development of new anticancer therapy.
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Joanna Kononczuk, Arkadiusz Surazynski, Urszula Czyzewska, Izabela Prokop, Michal Tomczyk, Jerzy Palka and Wojciech Miltyk , αIIbβ3-integrin Ligands: Abciximab and Eptifibatide as Proapoptotic Factors in MCF-7 Human Breast Cancer Cells, Current Drug Targets 2015; 16 (13) . https://dx.doi.org/10.2174/1389450115666140804220441
DOI https://dx.doi.org/10.2174/1389450115666140804220441 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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