Prdm14 Mediates Chemosensitivity And Glycolysis In Drug-Resistant A549/Cisplatin Cells And Their Progenitor A549 Human Lung Adenocarcinoma Cells

Recent studies have reported that aberrant PR domain zinc finger protein 14 (PRDM14) expression is associated with the therapeutic sensitivity of cancer cells to drugs. However, its role in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to determine the functions of knockdown or overexpression of PRDM14 in the chemosensitivity and glycolysis of LUAD cells. PRDM14 expression was analyzed in lung cancer tissues from patients resistant and sensitive to cisplatin (DDP), as well as in LUAD cell lines A549 and DDP-resistant A549 (A549/DDP) using reverse transcription quantitative-PCR and western blotting. Additionally, apoptosis was analyzed by flow cytometry, and flow cytometry and biochemical analysis was used to analyze glycolysis, indicated by glucose uptake and lactate release. The results of the present study demonstrated that PRDM14 expression was upregulated in patients with DDP-resistant LUAD and DDP-resistant cell lines. Overexpression of PRDM14 suppressed the sensitivity of A549 cells to DDP and silencing of PRDM14 using shRNA targeting PRDM14 promoted the sensitivity of A549/DDP cells to DDP, compared with that in the respective control groups. In mice with xenograft tumors, knockdown of PRDM14 using shRNA targeting PRDM14 inhibited the A549/DDP cell-derived tumor growth compared with scramble shRNA. The results of the glycolysis assays demonstrated that PRDM14 silencing inhibited glucose uptake, lactate release and glucose transporter 1 expression in A549/DDP cells compared with those in the control cells. PRDM14 overexpression relieved the inhibitory effects of 3-bromopyruvate, a potent glycolytic inhibitor for glycolysis, on glucose uptake and lactate release in A549 cells compared with those in the control cells. Therefore, the results of the present study suggested that PRDM14 may inhibit the chemosensitivity and promote glycolysis in human LUAD cells.