Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro.
Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro.
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应用线粒体丙酮酸载体阻断剂 UK5099 在体外 LnCap 前列腺癌细胞中产生代谢重编程和更强的干细胞样特性。
DOI：
10.18632/oncotarget.5386
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发表时间：
2015-11-10
期刊：
影响因子：
--
通讯作者：
Suo Z
中科院分区：
文献类型：
--
作者：
Zhong Y;Li X;Yu D;Li X;Li Y;Long Y;Yuan Y;Ji Z;Zhang M;Wen JG;Nesland JM;Suo Z
有氧糖酵解是癌细胞和真核细胞的重要标志之一。在本研究中，我们研究了UK5099阻断线粒体丙酮酸载体（MPC）与前列腺癌细胞代谢改变和干性表型之间的关系。研究发现，阻断丙酮酸转运至线粒体会减弱线粒体氧化磷酸化 (OXPHOS) 并增加糖酵解。 UK5099 处理的细胞显示出显着更高的侧群 (SP) 分数比例，并表达更高水平的干性标记 Oct3/4 和 Nanog。化学敏感性检查显示，与未处理的细胞相比，经过 UK5099 处理的细胞对化疗的抵抗力更强。这些结果表明体外 LnCap 细胞的代谢重编程和干细胞样表型之间可能存在密切联系。我们认为 MPC 阻断剂 (UK5099) 的应用可能是 Warburg 效应研究的理想模型，因为它减弱线粒体 OXPHOS 并增加有氧糖酵解，这种现象通常反映在 Warburg 效应中。我们得出的结论是，线粒体 OXPHOS 受损和糖酵解上调与前列腺癌细胞中的干细胞表型转变有关。
Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells.