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Beclin 1 表达抑制通过线粒体依赖途径增强人卵巢癌 SKOV3/DDP 细胞顺铂诱导的细胞凋亡。

Inhibition of Beclin 1 expression enhances cisplatin-induced apoptosis through a mitochondrial-dependent pathway in human ovarian cancer SKOV3/DDP cells.

机构信息

Department of Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China.

出版信息

Oncol Res. 2014;21(5):261-9. doi: 10.3727/096504014X13946388748992.

Abstract

The purpose of this study was to determine the influence of autophagy on cisplatin-induced ovarian cancer SKOV3/DDP cell line death through regulation of the expression of the autophagy gene, Beclin 1, and to explore the potential mechanism underlying the relationship between autophagy and apoptosis. When compared with a blank control group, the proportion of apoptotic cells undergoing Beclin 1 interfering increased significantly after cisplatin treatment, accompanied by reduction in mitochondrial membrane potential, increase in activities of caspase-9/3 and cytoplasmic cytochrome C, elevation of Bax expression, and reduction in Bcl-2 expression. However, the proportion of apoptotic cells with Beclin 1 overexpression reduced. These findings suggest that Beclin 1 plays an important role in the regulation of potent antitumor activity through a mitochondrial-dependent pathway in SKOV3/DDP cell line, and inhibition of Beclin 1 expression may become a new target for the sensitization therapy of ovarian cancer with cisplatin.

摘要

本研究旨在通过调节自噬基因 Beclin 1 的表达来确定自噬对顺铂诱导的卵巢癌 SKOV3/DDP 细胞系死亡的影响,并探讨自噬与细胞凋亡之间的潜在关系。与空白对照组相比,顺铂处理后 Beclin 1 干扰的凋亡细胞比例明显增加,同时伴随着线粒体膜电位降低、半胱氨酸天冬氨酸蛋白酶-9/3 和细胞质细胞色素 C 活性增加、Bax 表达升高和 Bcl-2 表达降低。然而,Beclin 1 过表达的凋亡细胞比例减少。这些发现表明,Beclin 1 通过线粒体依赖性途径在 SKOV3/DDP 细胞系中发挥重要作用,调节抗肿瘤活性,抑制 Beclin 1 表达可能成为顺铂治疗卵巢癌增敏治疗的新靶点。

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