Sun Li, Yin Yajie, Clark Leslie H, Sun Wenchuan, Sullivan Stephanie A, Tran Arthur-Quan, Han Jianjun, Zhang Lu, Guo Hui, Madugu Esther, Pan Tommy, Jackson Amanda L, Kilgore Joshua, Jones Hannah M, Gilliam Timothy P, Zhou Chunxiao, Bae-Jump Victoria L
Department of Gynecologic Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, People's Republic of China.
Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Oncotarget. 2017 Jun 29;8(38):63551-63561. doi: 10.18632/oncotarget.18854. eCollection 2017 Sep 8.
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.
癌细胞代谢对于支持细胞生长和细胞分裂的生物合成需求以及维持氧化还原稳态是必需的。本研究旨在测试葡萄糖和谷氨酰胺对卵巢癌细胞生长的影响，并探索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、细胞凋亡和ATP生成，对SKOV3、IGROV - 1和Hey卵巢癌细胞系进行葡萄糖、丙酮酸和谷氨酰胺依赖性检测。通过MTT法测定，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）诱导细胞凋亡，导致G1期细胞周期停滞并降低糖酵解活性。此外，2 - DG与低剂量的氨氧乙酸（AOA）联合使用可协同增加卵巢癌细胞系对2 - DG抑制细胞生长的敏感性。这些研究表明，双重抑制糖酵解和谷氨酰胺分解可能是治疗卵巢癌的一种有前景治疗策略。
