Abstract:
Objective: To investigate the role of mitochondrial transcription factor A (TFAM) in platinum-resistant ovarian cancer cells, with a focus on its effects on metabolic reprogramming and sensitivity to platinum-based drugs.
Objective: To investigate the role of mitochondrial transcription factor A (TFAM) in platinum-resistant ovarian cancer cells, with a focus on its effects on metabolic reprogramming and sensitivity to platinum-based drugs.
Methods: Mitochondrial function and metabolic characteristics of platinum-resistant ovarian cancer cells were first analyzed. Subsequently, a TFAM-overexpressing cell model was established to assess its impact on platinum sensitivity, mitochondrial function, and aerobic glycolysis, with further analysis of glycolytic enzyme and drug resistance protein expression.
Results: Platinum-resistant ovarian cancer cells showed significant mitochondrial dysfunction (reduced oxygen consumption rate) and enhanced aerobic glycolysis (increased extracellular acidification rate, glucose uptake, and lactate production). TFAM was downregulated in resistant cells, while TFAM overexpression significantly enhanced platinum sensitivity (p < 0.01), restored mitochondrial function, and inhibited aerobic glycolysis. Expression levels of glycolytic enzymes and drug resistance proteins were also downregulated (p < 0.05).
Conclusion: TFAM downregulation is associated with suppressed oxidative phosphorylation and enhanced aerobic glycolysis in platinum-resistant ovarian cancer cells. TFAM overexpression can restore cellular dependence on oxidative phosphorylation and increase platinum sensitivity, suggesting TFAM as a potential therapeutic target to counteract platinum resistance.
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