Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation.

Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation.
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乳酸酸中毒将癌细胞从有氧糖酵解转变回占主导地位的氧化磷酸化

DOI:
10.18632/oncotarget.9746
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发表时间:
2016-06-28
期刊:
影响因子:
--
通讯作者:
Hu X
Hu X
中科院分区:
其他
文献类型:
--
作者:
Wu H;Ying M;Hu X

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虽然正常细胞转化为癌细胞伴随着从氧化磷酸化(OXPHOS)到有氧糖酵解的转变,但有趣的是,癌细胞是否可以从瓦尔堡效应恢复到OXPHOS。我们以前的工作表明,当癌细胞暴露于乳酸性酸中毒时,它们会恢复为OXPHOS,这是肿瘤环境中的一个常见因素。然而,除非从糖酵解和OXPHOS的ATP输出被定量测定,否则不能得出结论。在这里,我们定量测量ATP生成糖酵解和OXPHOS在9个随机选择的癌细胞系。在没有乳酸酸中毒的情况下,糖酵解和OXPHOS分别产生总ATP的23.7%-52.2%和47.8%-76.3%;在乳酸酸中毒(20 mM乳酸盐,pH 6.7)的情况下,糖酵解和OXPHOS分别产生总ATP的5.7%-13.4%和86.6%-94.3%。我们的结论是,乳酸酸中毒下的癌细胞从瓦尔堡效应恢复到OXPHOS表型。
While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7%− 52.2% and 47.8%− 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7%− 13.4% and 86.6%− 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype.
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