Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer.

Abstract

In this study, we investigated the effects of tumor necrosis factor receptor-associated protein 1 (TRAP1) on aerobic glycolysis in cisplatin-resistant lung cancer cells and explored the underlying mechanism. TRAP1 expression levels were determined in cisplatin-resistant lung cancer tissues and A549/CDDP cells. Subsequently, TRAP1 expression in A549/CDDP cells was silenced via small interfering RNA transfection. Moreover, changes in lactate content, glucose consumption, expression levels of lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2), and sensitivity to cisplatin were analyzed. Specifically, the Wnt/β-catenin signaling pathway was examined using the Wnt/β-catenin activator, BML-284. TRAP1 expression levels were higher in cisplatin-resistant tissues and A549/CDDP cells than in cisplatin-sensitive tissues and A549 cells (P<0.05). Moreover, the lactate content, glucose consumption, LDHA, HK2, PKM2 expression levels, and half-maximal inhibitory concentration of cisplatin were all significantly decreased after TRAP1 silencing (P<0.05). Compared with A549 cells, the Wnt/β-catenin pathway was activated in A549/CDDP cells, which was inhibited via TRAP1 silencing. BML-284 reversed the effects of TRAP1 silencing on the aerobic glycolysis and cisplatin sensitivity of A549/CDDP cells. Our findings suggest that TRAP1 affects the cisplatin resistance of lung cancer, possibly by regulating aerobic glycolysis via the Wnt/β-catenin pathway.