Table 1.
Metabolic changes in epithelial ovarian cancer: in vitro studies
| Study models | Major findings | Interpretation | References | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
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| Glycolytic-related findings | OXPHOS-related findings | |||||||||
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| Glycolytic enzymes | Basal ECAR | Glycolytic capacity | Others | OXPHOS enzymes | Basal OCR | Respiratory capacity | Others | |||
| -Human ovarian HGSC cells (OVCAR3 (S), human OCCC cells (TOV-21G (C)) | ↑↑ PFKP | (S): ↑↑ PDHB, IDH2, IDH3A, OGDHL, ND2, UQCRH | -HGSC and clear cells had an increase in mitochondrial complex I and complex III activity compared to normal cells. | [26] | ||||||
| ↓↓ CYB | ||||||||||
| -Normal ovarian epithelial cells (control) | ↑↑ PKM | (C): ↑↑ IDH2, OGDHL, ND2, CYB | ||||||||
| ↓↓ IDH3A | ||||||||||
| -Human HGSC cells (OVCAR3) | ↔ | ↔ | ↑↑ | ↑↑ | -Human OCCC had an increase in both glycolysis and OXPHOS metabolism compared to other carcinoma and normal cells, while HGSC had higher OXPHOS only when compared to other carcinoma and normal cells. | [25] | ||||
| -Normal ovarian epithelial cells (control) | ||||||||||
| -Human HGSC cells (OVCAR3) | ↔ | ↔ | ↑↑ | ↑↑ | ||||||
| -Human ovarian carcinoma cells OVCA420 (control) | ||||||||||
| -Human OCCC cells (ES-2, TOV-21G) | ↑↑ (ES2) | ↑↑ | ↑↑ | ↑ (ES2) | ||||||
| -Normal ovarian epithelial cells (control) | ↑ (TOV-21G) | ↑↑ (TOV-21G) | ||||||||
| -Human OCCC cells (ES-2, TOV-21G) | ↑ (ES2) | ↔ (ES2) | ↑↑ | ↑↑ | ||||||
| -Human non-OCCC cells, OVCA420 (control) | ↔ (TOV-21G) | ↑↑ (TOV-21G) | ||||||||
| -Human ovarian E/OCCC cells (SKOV3) | ↓↓ PFKP | ↑ PDHB | -Endometrioid or OCCC may have shown glycolysis impairment. | [26] | ||||||
| -Normal ovarian epithelial cells (control) | ↑↑ PKM | ↔ IDH2 | ||||||||
| ↑↑ IDH3A, IDH3B | ||||||||||
| ↔ OGDHL | ||||||||||
| ↑↑ ND2, ND5, CYB | ||||||||||
| ↓↓ UQCRH | ||||||||||
| -Human ovarian carcinoma cells (OVCA420, OVCA429, OVCA433, DOV-13) | ↓ (DOV13) | ↑↑* | ↑↑* | ↓↓ (OVCA420, OVCA433) | -Most human nonspecific adenocarcinoma cells had higher OXPHOS than normal cells. | [25] | ||||
| -Normal ovarian epithelial cells (control) | ||||||||||
| -More invasive human E/OCCC (SKOV3, SKOV3ip1) | ↔ lactate | ↑ | ↑ | ↑ pyruvate uptake | -More invasive human E/OCCC cells had higher OXPHOS compared to less invasive HGSCs. | [28] | ||||
| -Less invasive human HGSC (OVCAR3) (control) | ↑ ATP | |||||||||
| Mouse ovarian surface epithelial (MOSE) cells | ↑ | ↑↑ glucose uptake | ↑ PDK1 | ↓ | ↓ ATP | -Mouse aggressive ovarian cells had higher glycolysis and lower OXPHOS compared to mouse benign ovarian epithelial cells. | [27] | |||
| -MOSE-L = late-aggressive phenotype | ↑↑ lactate | ↑ CS | ||||||||
| -MOSE-E = early benign phenotype (control) | ↔ PDH | |||||||||
The superscript *indicates all cell lines except OVCA420. The arrow ↑ or ↓ denotes significant increase or decrease in the metabolic-related finding with a P value <0.05. The arrow ↑↑ or ↓↓ denotes significant increase or decrease in the metabolic-related finding with a P value <0.01. Abbreviations: CS; citrate synthase, CYB; cytochrome b reductase 1, E; endometrioid adenocarcinoma, ECAR; extracellular acidification rate, HGSC; high-grade serous carcinoma, IDH2; isocitrate dehydrogenase [NADP], IDH3A; isocitrate dehydrogenase [NAD] subunit alpha, IDH3B; isocitrate dehydrogenase [NAD] subunit beta, ND; NADH-ubiquinone oxidoreductase, OCCC; ovarian clear cell carcinoma, OCR; oxygen consumption rate, OGDHL; 2-oxoglutarate dehydrogenase-like, OXPHOS; oxidative phosphorylation, PDH; pyruvate dehydrogenase, PDK1; pyruvate dehydrogenase kinase 1, PFKP; phosphofructokinase platelet, PKM; pyruvate kinase muscle isozyme, UQCRH; ubiquinol-cytochrome c reductase hinge protein.