PKM2对黑色素瘤细胞侵袭与迁移及巨噬细胞M2转变的影响OACSTPCD

Objective To investigate the expression of PKM2 in melanoma and its correlation with progno-sis,and to elucidate how PKM2 affects melanoma invasion and migration through the glycolytic pathway and its impact on macrophage M2 transformation.Methods The expression of PKM2 in melanoma was analyzed by TCGA database and immunohistochemistry;the effects of PKM2 on the glycolytic process of melanoma cells were analyzed by gene overexpression,knockdown and ECAR techniques;the effect of PKM2 on the inva-sion and migration of melanoma cells were verified by scratch and Transwell experiments;the effect of PKM2 on macrophage M2 transformation was elucidated by cell co-culture.Results The TCGA database showed that PKM2 mRNA levels were significantly higher in melanoma tissues compared with normal tissues(P<0.05),and survival rate of patients with high PKM2 expression levels was lower than that of patients with low/medium expression(P=0.001 8);immunohistochemical staining showed that PKM2 scores in patients with metastases from melanoma were significantly higher than those in patients without metastatic patients,and the difference was statistically significant(P<0.05).After knocking down PKM2 expression,melanoma cell glycolytic capacity,glycolytic capacity and lactate level were significantly reduced(P<0.05).The results of cell migration assay showed that the migration and invasion ability of melanoma cells were significantly re-duced after knocking down PKM2 expression,and the addition of lactic acid partially reversed the phenome-non.The levels of TNF-α and iNOS of melanoma macrophages in PKM2 overexpressing group were lower than those in the control group,while the levels of CD206 and CD163 were higher than those in the control group,and the differences had statistical significance(P<0.05);the TNF-α and iNOS levels of knockdown PKM2 group on melanoma macrophages were higher than those of the control group,while CD206 and CD163 were lower than those of the control group,and the differences were all statistically significant(P<0.05).Conclusion PKM2 promotes the invasion and migration of melanoma by influencing the glycolysis process,and promotes the M2 transformation of macrophages in the tumor microenvironment,making it a potential target for metabolic therapy of melanoma.