. 2021 Sep 15;13(9):9950–9973.

Table 5.

The comparative effects of glycolytic and OXPHOS interventions on epithelial ovarian cancer cell metabolism and its invasive properties: in vitro studies

Human ovarian carcinoma cells	Intervention (dose, duration)	Major findings												Interpretation	References

		Glycolytic-related findings				OXPHOS-related findings				Oncological outcomes

		Glucose uptake	Glycolytic enzymes	Lactate	Others	OXPHOS enzymes	OCR	ROS	Other	Growth	Invasion	Migration	Others
A2780, SKOV3	-PTTG suppression (PTTG-shRNA, 25 mmol/L, 48 h)	↓	↓ HK	↓	↓ Glut1		↑	↑	↑ ATP	↓				-PTTG suppression caused a decrease in glycolysis and an increase in OXPHOS, and resulted in decreased cell proliferation.	[34]
			↓ PFK		↓ c-myc
			↓ PKM2
			↓ LDHA
	-PTTG-shRNA +2-DG (100 mM, 12-72 h)				↓ decreased ECAR		↑						↑ decreased viability
	-Control-shRNA +2-DG
	-PTTG-shRNA + oligomycin (2 µg/mL, 12-72 h)				↔ ECAR		↓↓						↓ viability
	-Control-shRNA + oligomycin
Hey, SKOV3	-JQ1 (500-1000 nM, 24 h)	↓	↓ LDHA	↓	↓ c-myc			↓	↓ ATP	↓			↑ apoptosis	-JQ1 inhibited c-myc, glycolysis, and cell proliferation.	[43]
Hey, SKOV3	-JQ1 (500-1000 nM, 24 h)	↓	↓ LDHA	↓	↓ c-myc			↓	↓ ATP	↓			↔ necrosis	-JQ1 inhibited c-myc, glycolysis, and cell proliferation.	[43]
CP90, OV90	-MICU1 silencing (siRNA-MICU1 transfection, 48-96 h)			↓		↓ p-PDH	↑	↑	↑ complex III	↓	↓	↓	↓ motility	-Silencing MICU1 decreased glycolysis, cell growth, and invasiveness but increased OXPHOS shifting enzymes and OXPHOS metabolism.	[45]
CP90, OV90	-MICU1 silencing (siRNA-MICU1 transfection, 48-96 h)			↓		↑ PDH	↑	↑	↑ complex III	↓	↓	↓	↓ motility		[45]
OVCAR3, SKOV3	-MPC1 inhibitor (20 µM, 1 week)	↑			↑ ECAR				↓ mt-pyruvate	↔		↑	↑ stemness markers	-MPC1 inhibitor resulted in increased glycolysis, stemness markers, migration, and motility.	[48]
									↓ ATP				↑ motility
									↓ ATP				↑ viability
A549, SKOV3	-FAM210B silencing (siRNA transfection, 48 h)	↓		↓	↓ ECAR	↓ PDK4	↑	↔				↑	↑ viability	-Loss of mitochondrial protein FAM210B caused an increased OXPHOS and promoted cell aggressiveness.	[64]
A549, SKOV3	-FAM210B silencing (siRNA transfection, 48 h)	↓		↓	↓ ECAR	↓ p-PDH	↑	↔				↑	↑ EMT		[64]
OVCAR3, SKOV3	-NOS inhibitor (10 mM, 48 h)	↓	↑ HK2	↓			↓	↑	↓ pyruvate uptake	↓				-NO could induce glycolysis, impaired OXPHOS, and cell growth.	[46]
OVCAR3, SKOV3	-NO donor (100 µM, 24 h)	↑		↑				↓	↓ complex II, III, IV						[46]
CP70, SKOV3	-PKM2 inhibitor, shikonin (3 µM, 5 h)	↓	↓ PKM2	↓	↓ ECAR		↔			↓		↓		-Inhibition of PKM2 caused a decrease in glycolysis, cell proliferation, and migration.	[47]
CP70, SKOV3	-Control (7 h)														[47]
SKOV3	-Ad-CHIP (CHIP 5 µM, 4 h)		↔ HK		↓ pyruvate		↑			↓				-CHIP decreased glycolysis and inhibited cell proliferation.	[44]
			↓ PKM2		↓ ECAR
			↓ PKM2		↓ glycolytic capacity

The arrow ↑ or ↓ denotes a significant increase or decrease in the metabolic-related finding or the cells’ oncologic activities, i.e. cell growth, invasion, migration and viability, with a P value <0.05. The arrow ↑↑ or ↓↓ denotes a significant increase or decrease in the metabolic-related finding or the cells’ oncologic activities with a P value <0.01. Abbreviations: Ad-; adenovirus infected, CHIP; carboxyl terminus of Hsc70-interacting protein, ECAR; extracellular acidification rate, EMT; epithelial-mesenchymal transition, HK; hexokinase, LDH; lactate dehydrogenase, MICU1; mitochondrial calcium uptake 1, miR; microRNA, MPC; mitochondrial pyruvate carrier, mt-; mitochondrial, NO; nitric oxide, NOS; nitric oxide synthase, OXPHOS; oxidative phosphorylation, OCR; oxygen consumption rate, p-PDH; phosphorylated-pyruvate dehydrogenase, PDH; pyruvate dehydrogenase, PDK; pyruvate dehydrogenase kinase, PFK; phosphofructokinase, PKM2; pyruvate kinase M2, PTTG; pituitary tumor-transforming gene, ROS; reactive oxygen species.