RESUMO
Aim To investigate the mechanism of heparin-binding epidermal growth factor (HBEGF) in upregulating the expression of programmed death ligand 1 (PD-L1) in glioma cells by regulating leukemia inhibitory factor (LIF). Methods Pearson analysis was used to analyze the correlation between HBEGF, LIF and PD-L1 mRNA in primary gliomas, U251 and U87 cells were treated with HBEGF neutralizing antibody and HBEGF was added after HBEGF knockout, the mRNA and protein levels of LIF and PD-L1 were detected by real-time fluorescence quantitative PCR (RT-qPCR) and Western blot, HBEGF knockout cells were added with LIF neutralizing antibody on the basis of adding HBEGF, and the levels of PD-L1 mRNA and protein were detected. Results Pearson analysis showed that HBEGF, LIF, and PD-L1 mRNA were positively correlated (P < 0.05). After adding HBEGF neutralizing antibody to U251 and U87 cells, the mRNA and protein levels of LIF and PD-L1 gradually decreased with cell passage (P < 0.05). After HBEGF knockout, the mRNA and protein levels of LIF and PD-L1 decreased (P < 0.05), and the mRNA and protein levels of LIF and PD-L1 increased after HBEGF was added (P < 0.05). In HBEGF knockout cell lines, the levels of PD-L1 mRNA and protein were up-regulated after HBEGF was added (P<0.05), and the levels of PD-L1 mRNA and protein was down-regulated by LIF neutralizing antibody (P < 0.05). Conclusion The partial induction of LIF by HBEGF in glioblastoma is an intermediate process for HBEGF to maintain PD-L1 expression.