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WP 631与埃坡霉素B联合介导的半胱天冬酶和活性氧依赖性作用机制

Caspases and ROS - dependent mechanism of action mediated by combination of WP 631 and epothilone B.

作者信息

Rogalska Aneta, Bukowska Barbara, Marczak Agnieszka

机构信息

Department of Thermo biology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

出版信息

Anticancer Agents Med Chem. 2014;14(9):1261-70. doi: 10.2174/1871520614666140608150807.

DOI:10.2174/1871520614666140608150807
PMID:24913659
Abstract

In this article, the synergistic effects of WP 631 and epothilone B (Epo B) combination in human ovarian cancer cells (SKOV-3) cells are investigated and the reasons for the exact mechanisms of action of both drugs co-administered are explained. Compared with single drugs, the combination treatment significantly enhances apoptosis as confirmed by increases in caspases (-8, -9, -3) activity, ROS level and DNA damage and decreases in mitochondrial membrane potential. The combination of the compounds activated both caspase - 8 and -9, indicates that both pathways of apoptosis, extrinsic (induced by the effect of Epo B) and intrinsic (triggered mainly by WP 631) participate in the proposed treatment. Thus, the results of this study strongly suggest a synergistic action of the combined treatment with WP 631 and Epo B in SKOV-3 cells death induction.

摘要

在本文中,研究了WP 631与埃坡霉素B(Epo B)联合应用对人卵巢癌细胞(SKOV-3)的协同作用,并解释了两种药物联合给药确切作用机制的原因。与单一药物相比,联合治疗显著增强了细胞凋亡,这通过半胱天冬酶(-8、-9、-3)活性、活性氧水平和DNA损伤的增加以及线粒体膜电位的降低得到证实。化合物的联合激活了半胱天冬酶-8和-9,表明细胞凋亡的两条途径,即外在途径(由Epo B的作用诱导)和内在途径(主要由WP 631触发)都参与了所提出的治疗。因此,本研究结果强烈表明WP 631和Epo B联合治疗在诱导SKOV-3细胞死亡方面具有协同作用。

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