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Oxidative phosphorylation activation is an important characteristic of DOX resistance in hepatocellular carcinoma cells.
- Source :
-
Cell Communication & Signaling . 2/5/2018, Vol. 16, p1-1. 1p. - Publication Year :
- 2018
-
Abstract
- Background: Despite the implications for tumor growth and cancer drug resistance, the mechanisms underlying differences in energy metabolism among cells remain unclear. Methods: To analyze differences between cell types, cell viability, ATP and α-ketoglutaric acid levels, the oxygen consumption rate and extracellular acidification rate, and the expression of key enzymes involved in α-KG metabolism and transfer were examined. Additionally, UPLC-MS/MS was used to determine the doxorubicin (DOX) content in SMMC-7721 and SMMC-7721/DOX cells. Results: We found that energy metabolism in SMMC-7721 cells is mainly dependent on the glycolysis pathway, whereas SMMC-7721/DOX cells depend more heavily on the oxidative phosphorylation pathway. Cell viability and intracellular ATP levels in SMMC-7721/DOX cells were significantly reduced by rotenone and oligomycin, inhibitors of oxidative phosphorylation. However, SMMC-7721 cell properties were more strongly influenced by an inhibitor of glycolysis, 2-deoxy-d-glucose. Furthermore, the suppressive effect of α-KG on ATP synthase plays an important role in the low levels of oxidative phosphorylation in SMMC-7721 cells; this effect could be strengthened by the metabolic poison methotrexate and reversed by l-(−)-malic acid, an accelerator of the malate-aspartate cycle. Conclusions: The inhibitory effect of α-KG on ATP synthase was uncoupled with the tricarboxylic acid cycle and oxidative phosphorylation in SMMC-7721 cells; accordingly, energy metabolism was mainly determined by glycolysis. In drug-resistant cells, a remarkable reduction in the inhibitory effects of α-KG on ATP synthase resulted in better coordination among the TCA cycle, oxidative phosphorylation, and glycolysis, providing novel potential strategies for clinical treatment of liver cancer resistance. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1478811X
- Volume :
- 16
- Database :
- Academic Search Index
- Journal :
- Cell Communication & Signaling
- Publication Type :
- Academic Journal
- Accession number :
- 127809218
- Full Text :
- https://doi.org/10.1186/s12964-018-0217-2