Table 6.
The comparative effects of glycolytic and OXPHOS interventions on epithelial ovarian cancer cell metabolism and invasive properties: in vivo studies
| Study in mouse models | Intervention (dose, duration) | Major findings | Interpretation | References | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||
| Glycolytic-related findings | OXPHOS-related findings | Oncological outcome-related findings | |||||||||
|
|
|
|
|||||||||
| Glycolytic enzymes | Others | OXPHOS enzymes | Metabolites | Others | Growth | Volume/weight | Others | ||||
| Ovaries intrabursally implanted with OV90 | -MICU1 silencing (shMICU1 transfection, 48-72 h) | ↓ LDH | ↓ lactate | ↓ p-PDH | ↓ | ↓ | ↑ apoptosis | -Silencing MICU1 caused decreasing glycolysis, tumor growth, and mouse survival. | [45] | ||
| ↑ PDH | ↑ median survival | ||||||||||
| Serous EOC with somatic deletion of Brca1 and p53 inactivation | -High-fat diet (obese) | ↓ F6P, pyruvate | ↑ succinate | ↑ | -Obese mice had less glycolytic activity but had more tumor growth than lean mice. | [50] | |||||
| -Low-fat diet (control) | ↓ fumarate, malate | ||||||||||
| -Metformin (200 mg/kg, oral gavage × 4 weeks) in obese mice | ↑ G6P, F6P, FBP, 2,3-DPG, PEP, lactate | ↑ α-ketoglutarate, fumarate, malate | ↓ | ↓ | ↑ caspase-3 | ||||||
| ↓ VEGF | -Metformin induced glycolysis, decreased angiogenesis, cell proliferation, and invasive properties. | ||||||||||
| -Metformin (200 mg/kg, oral gavage × 4 weeks) in lean mice (control) | ↓ succinate | ↓ MMP 9 | |||||||||
| ID8 cells intraperitoneal injection | -SP-/- (SPARC gene) | ↑ HK2 | ↑ G6P, F6P, pyruvate, lactate | ↑ SUCLG1, SUCLG2, ME2, IDH1 | ↑ succinate | ↑ ROS | ↑ | -Absence of SPARC genes increased glycolysis and OXPHOS activity and supported tumor growth. | [49] | ||
| -SP+/+ (control) | ↑ TPI1 | ↓ fumarate, citrate | |||||||||
| ↑ PGK1 | ↑ complex I, III, IV, V | ||||||||||
| ↑ PHGDH | |||||||||||
The arrow ↑ or ↓ denotes a significant increase or decrease in the metabolic-related finding or tumor oncologic activities, with a P value <0.05. Abbreviations: 2,3-DPG; 2,3-diphosphoglycerate, EOC; epithelial ovarian cancer, F6P; fructose-6-phosphate, FBP; fructose 1,6-bisphosphate, G6P; glucose-6-phosphate, HK2; hexokinase 2, IDH; isocitrate dehydrogenase, ip; intraperitoneal, LDH; lactate dehydrogenase, ME; malic enzyme, MICU1; mitochondrial calcium uptake 1, MMP; matrix metalloproteinase, OXPHOS; oxidative phosphorylation, p-PDH; phosphorylated-pyruvate dehydrogenase, PDH; pyruvate dehydrogenase, PEP; phosphoenolpyruvate, PGK1; phosphoglycerate kinase 1, PHGDH; phosphoglycerate dehydrogenase, ROS; reactive oxygen species, SPARC; secreted protein acidic and rich in cysteine, SUCLG; succinyl-CoA ligase, TPI1; triosephosphate isomerase, VEGF; vascular endothelial growth factor.