二氯乙酸改变瓦博格代谢，抑制细胞生长，并增加人 A549 和 H1299 NSC 肺癌细胞的 X 射线敏感性。
Dichloroacetate alters Warburg metabolism, inhibits cell growth, and increases the X-ray sensitivity of human A549 and H1299 NSC lung cancer cells.
机构信息
Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA.
Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
出版信息
Free Radic Biol Med. 2015 Dec;89:263-73. doi: 10.1016/j.freeradbiomed.2015.08.006. Epub 2015 Sep 21.
We investigated whether altering Warburg metabolism (aerobic glycolysis) by treatment with the metabolic agent dichloroacetate (DCA) could increase the X-ray-induced cell killing of the radiation-resistant human non-small-cell lung cancer (NSCLC) cell lines A549 and H1299. Treatment with 50mM DCA decreased lactate production and glucose consumption in both A549 and H1299, clear indications of attenuated aerobic glycolysis. In addition, we found that DCA treatment also slowed cell growth, increased population-doubling time, and altered cell cycle distribution. Furthermore, we report that treatment with 50mM DCA significantly increased single and fractionated X-ray-induced cell killing of A549 and H1299 cells. Assay of DNA double-strand break repair by neutral comet assays demonstrated that DCA inhibited both the fast and the slow kinetics of X-ray-induced DSB repair in both A549 and H1299 NSCL cancer cells. Taken together the data suggest a correlation between an attenuated aerobic glycolysis and enhanced cytotoxicity and radiation-induced cell killing in radiation-resistant NSCLC cells.
我们研究了通过用代谢剂二氯乙酸（DCA）处理来改变沃伯格代谢（有氧糖酵解）是否可以增加耐辐射的人非小细胞肺癌（NSCLC）细胞系 A549 和 H1299 的 X 射线诱导的细胞杀伤。用 50mM DCA 处理可降低 A549 和 H1299 中的乳酸产生和葡萄糖消耗，这明显表明有氧糖酵解减弱。此外，我们发现 DCA 处理还会减缓细胞生长，增加倍增时间，并改变细胞周期分布。此外，我们报告称，用 50mM DCA 处理可显著增加 A549 和 H1299 细胞的单次和分次 X 射线诱导的细胞杀伤。中性彗星试验检测 DNA 双链断裂修复的试验表明，DCA 抑制了 A549 和 H1299 NSCLC 细胞中 X 射线诱导的 DSB 修复的快速和慢速动力学。总的来说，这些数据表明在耐辐射的 NSCLC 细胞中，有氧糖酵解减弱与细胞毒性增强和辐射诱导的细胞杀伤之间存在相关性。
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