Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer.
Dual inhibition of glycolysis and glutaminolysis as a therapeutic strategy in the treatment of ovarian cancer.
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DOI：
10.18632/oncotarget.18854
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Bae-Jump VL
中科院分区：
文献类型：
--
作者：
Sun L;Yin Y;Clark LH;Sun W;Sullivan SA;Tran AQ;Han J;Zhang L;Guo H;Madugu E;Pan T;Jackson AL;Kilgore J;Jones HM;Gilliam TP;Zhou C;Bae-Jump VL
需要癌细胞代谢来支持细胞生长和细胞分裂的生物合成需求，并维持还原氧化（氧化还原）稳态。本研究旨在检测葡萄糖和谷氨酰胺对卵巢癌细胞生长的影响，并探讨糖酵解和谷氨酰胺分解之间的相互关系。通过分析细胞毒性、细胞周期进程、凋亡和ATP产生来测定SKOV 3、IGF 3 -1和Hey卵巢癌细胞系的葡萄糖、丙酮酸和谷氨酰胺依赖性。MTT法显示，葡萄糖刺激细胞生长，而葡萄糖、谷氨酰胺和丙酮酸的组合对细胞增殖的刺激作用最大。此外，2-脱氧葡萄糖（2-DG）和3-溴丙酮酸（3-BP）可诱导细胞凋亡，使细胞周期阻滞于G1期，糖酵解活性降低。此外，2-DG与低剂量的氨氧基乙酸（AOA）的组合协同增加了卵巢癌细胞系中细胞生长抑制对2-DG的敏感性。这些研究表明，双重抑制糖酵解和β-氨基丁酸解可能是治疗卵巢癌的一种有前途的治疗策略。
Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division, and to maintain reduction oxidaton (redox) homeostasis. This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth and explore the inter-relationship between glycolysis and glutaminolysis. The SKOV3, IGROV-1 and Hey ovarian cancer cell lines were assayed for glucose, pyruvate and glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis and ATP production. As determined by MTT assay, glucose stimulated cell growth while the combination of glucose, glutamine and pyruvate resulted in the greatest stimulation of cell proliferation. Furthermore, 2-deoxy-glucose (2-DG) and 3-bromopyruvate (3-BP) induced apoptosis, caused G1 phase cell cycle arrest and reduced glycolytic activity. Moreover, 2-DG in combination with a low dose of aminooxyacetate (AOA) synergistically increased the sensitivity to 2-DG in the inhibition of cell growth in the ovarian cancer cell lines. These studies suggest that dual inhibition of glycolysis and glutaminolysis may be a promising therapeutic strategy for the treatment of ovarian cancer.
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影响因子：
4.7
作者：
Fajas L
通讯作者：
Fajas L
DOI：
10.1634/theoncologist.2009-0300
发表时间：
2010
期刊：
The oncologist
影响因子：
--
作者：
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作者：
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作者：
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通讯作者：
Schmelz EM
影响因子：
4.7
作者：
Kim, Choon-Young;Jeong, Shin Young;Lee, Jaetae
通讯作者：
Lee, Jaetae