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首页> 外文期刊>Journal of biochemical and molecular toxicology >2-Deoxy-D-Glucose Sensitizes Human Ovarian Cancer Cells to Cisplatin by Increasing ER Stress and Decreasing ATP Stores in Acidic Vesicles
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2-Deoxy-D-Glucose Sensitizes Human Ovarian Cancer Cells to Cisplatin by Increasing ER Stress and Decreasing ATP Stores in Acidic Vesicles

机译：2-脱氧-D-葡萄糖通过增加内质网应激并减少酸性囊泡中的ATP储存，使人卵巢癌细胞对顺铂敏感。

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摘要

Cisplatin is a commonly used chemotherapeutic agent; however, the development of acquired resistance limits its application. Here, we demonstrate that 2-deoxy-D-glucose (2-DG) enhanced the antitumor effects of cisplatin in SKOV3 cells, which include inhibition of proliferation and promotion of apoptosis. Additionally, either cisplatin or 2-DG alone could upregulate the endoplasmic reticulum (ER) stress-associated protein glucose-regulated protein-78 (GRP78). Moreover, exposure to 2-DG increased the expression of GRP78 induced by cisplatin. Cisplatin also upregulated ER stress-associated apoptotic protein 153/C/EBP homology protein (CHOP) in SKOV3 cells. While treatment with 2-DG alone could not upregulate the CHOP expression, a combination of both 2-DG and cisplatin increased the protein levels of CHOP above those induced by Cisplatin alone. Finally, cisplatin mediated an increase in ATP stores within acidic vesicles, whereas 2-DG decreased this effect. These data demonstrate that 2-DG sensitizes SKOV3 cells to cisplatin by increasing ER stress and decreasing ATP stores in acidic vesicles. (C) 2015 Wiley Periodicals, Inc.
机译：顺铂是一种常用的化学治疗剂。但是，获得性抗性的发展限制了其应用。在这里，我们证明2-脱氧-D-葡萄糖（2-DG）增强了顺铂在SKOV3细胞中的抗肿瘤作用，包括抑制增殖和促进凋亡。另外，单独使用顺铂或2-DG均可上调内质网（ER）应激相关蛋白葡萄糖调节蛋白78（GRP78）。而且，暴露于2-DG增加了顺铂诱导的GRP78的表达。顺铂还上调了SKOV3细胞中与ER应激相关的凋亡蛋白153 / C / EBP同源蛋白（CHOP）。尽管仅用2-DG处理不能上调CHOP的表达，但将2-DG和顺铂联合使用可使CHOP的蛋白水平高于单独用顺铂诱导的水平。最后，顺铂介导了酸性囊泡中ATP储存的增加，而2-DG降低了这种作用。这些数据表明2-DG通过增加ER应激和减少酸性囊泡中的ATP储存使SKOV3细胞对顺铂敏感。 （C）2015威利期刊公司

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