Mitochondrial Enzymes Mediate Cisplatin Resistance in Hypopharyngeal Squamous Cell Carcinoma Cells

Abstract

Cisplatin, a widely used chemotherapeutic drug, faces significant challenges due to drug resistance, which hinders its clinical effectiveness. However, the molecular mechanism underlying cisplatin resistance remains unclear. Previous studies have shown that tumor cells rely on glycolysis for energy and nutrients due to mitochondrial dysfunction. Yet, limited research has explored changes in energy metabolism after the development of drug resistance in tumor cells. In this study, we investigated the relationship between changes in key enzymes involved in aerobic respiration in mitochondria and cisplatin resistance. Our findings revealed enhanced synthesis of citrate synthase (CS), succinate dehydrogenase (SD), and cytochrome oxidase (CCO) in drug-resistant cancer cells, with CCO showing the greatest increase. Notably, inhibiting CCO activity reversed drug resistance in cancer cells. These findings shed light on a new mechanism of cisplatin resistance related to energy metabolism and offer a promising approach to overcoming resistance and improving clinical anticancer effects.