Investigating the Mechanism of β-Elemene-Mediated LINC00511 Modulation to Suppress Cisplatin Resistance in Lung Cancer

Cisplatin resistance significantly limits the efficacy of chemotherapy in non-small cell lung cancer, necessitating the development of new strategies to overcome this barrier. This in vitro study aimed to elucidate the mechanism by which β-Ele reverses cisplatin resistance in lung adenocarcinoma cells via the LINC00511-mediated glycolysis and Wnt/β-catenin signaling pathways. The cisplatin-resistant human lung adenocarcinoma cell line (A549/DDP), with either LINC00511 overexpression or knockdown, was established through plasmid transfection. The transfection efficiency was evaluated using Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) to detect LINC00511 expression levels. Assessment via the 5-ethynyl-2'-deoxyuridine (EdU) assay indicated significant β-Ele-mediated inhibition of A549/DDP cell proliferation. Further RNA-seq analysis revealed that the inhibitory effect of β-Elemene on cisplatin resistance was closely associated with the interference of cellular glycolysis and the suppression of Wnt/β-catenin signaling pathway activation. Western blot analysis of key proteins, including glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), β-catenin, and glycogen synthase kinase 3β (GSK-3β), showed that β-Elemene reversed cisplatin resistance by inhibiting aerobic glycolysis and blocking the activation of the Wnt/β-catenin signaling pathway through downregulation of LINC00511. Collectively, these results demonstrate that β-Elemene overcomes cisplatin resistance in lung cancer by targeting LINC00511 and its associated aerobic glycolysis/Wnt/β-catenin pathway. This establishes a theoretical framework for future preclinical and clinical investigations while revealing potential therapeutic targets.