Guo Liyuan, Peng Yan, Li Yulian, Yao Jingping, Zhang Guangmei, Chen Jie, Wang Jing, Sui Lihua
Department of Obstetrics and Gynecology, Third Affiliated Hospital, Harbin Medical University, Harbin 150081, P.R. China.
Department of Health, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, P.R. China.
Oncol Lett. 2015 Mar;9(3):1359-1363. doi: 10.3892/ol.2015.2851. Epub 2015 Jan 7.
Resveratrol-bovine serum albumin nanoparticles (RES-BSANP) exhibit chemotherapeutic properties, which trigger apoptosis. The aim of the present study was to investigate the caspase-independent cell death pathway induced by RES-BSANP in human ovarian cancer SKOV3 cells and to analyze its mechanism. Morphological changes were observed by apoptotic body/cell nucleus DNA staining using inverted and fluorescence microscopy. The cell death pathway was determined by phosphatidylserine translocation. Western blot analysis was conducted to detect the activation of apoptosis-inducing factor (AIF), cytochrome (Cyto ) and B-cell lymphoma 2-associated X protein (Bax). Apoptotic body and nuclear condensation and fragmentation were observed simultaneously following treatment with RES-BSANP. RES-BSANP induced apoptosis in a dose-dependent manner in the human ovarian cancer SKOV3 cells. The translocation of AIF from the mitochondria to the cytoplasm occurred earlier than that of Cyto . In addition, Bax binding to the mitochondria was required for the release of AIF and Cyto from the mitochondria. The AIF apoptosis pathway may present an alternative caspase-dependent apoptosis pathway in human ovarian cell death induced by RES-BSANP. Elucidation of this pathway may be critical for the treatment of cancer using high doses of RES-BSANP.
白藜芦醇-牛血清白蛋白纳米粒(RES-BSANP)具有化疗特性,可引发细胞凋亡。本研究旨在探讨RES-BSANP在人卵巢癌SKOV3细胞中诱导的非半胱天冬酶依赖性细胞死亡途径并分析其机制。使用倒置显微镜和荧光显微镜通过凋亡小体/细胞核DNA染色观察形态学变化。通过磷脂酰丝氨酸易位确定细胞死亡途径。进行蛋白质免疫印迹分析以检测凋亡诱导因子(AIF)、细胞色素c(Cyto c)和B细胞淋巴瘤2相关X蛋白(Bax)的激活情况。用RES-BSANP处理后同时观察到凋亡小体以及细胞核浓缩和碎片化。RES-BSANP在人卵巢癌SKOV3细胞中以剂量依赖性方式诱导细胞凋亡。AIF从线粒体向细胞质的易位比Cyto c早发生。此外,Bax与线粒体的结合是AIF和Cyto c从线粒体释放所必需的。AIF凋亡途径可能是RES-BSANP诱导的人卵巢细胞死亡中一种替代的非半胱天冬酶依赖性凋亡途径。阐明该途径对于使用高剂量RES-BSANP治疗癌症可能至关重要。