丙酮酸脱氢酶激酶抑制剂促进食管鳞状细胞癌PD-L1的表达

Inhibitors of pyruvate dehydrogenase kinase promote PD-L1 expression in esophageal squamous cell carcinoma

目的探讨丙酮酸脱氢酶激酶(pyruvate dehydrogenase kinase,PDHK)抑制剂对食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)中PD-L1表达的影响及其可能的分子机制。方法Western blot和qRT-PCR检测PD-L1表达水平,流式细胞术和免疫荧光染色检测细胞膜上PD-L1的表达,SRB法检测细胞增殖,基因芯片数据及hTFtarget数据库预测PD-L1基因启动子区域结合的转录因子。结果PDHK抑制剂浓度依赖性上调ESCC细胞中PD-L1表达,同时在该浓度范围内PDHK抑制剂对ESCC细胞增殖无显著影响;基因芯片数据及hTFtarget数据库预测PDHK抑制剂可能通过转录因子NFATc1促进ESCC细胞中PD-L1的转录表达。结论PDHK抑制剂促进食管鳞状细胞癌表达PD-L1,转录因子NFATc1可能参与该过程。

Objective To explore the effect of pyruvate dehydrogenase kinase(PDHK)inhibitors on the expression of PD-L1 in esophageal squamous cell carcinoma(ESCC)and its possible molecular mechanisms Methods Western blotting and qRT-PCR were used to detect the expression level of PD-L1,flow cytometry and immunofluorescence staining were used to detect the expression of PD-L1 on the cell membrane,SRB method was used to detect cell proliferation,gene CHIP data and hTFtarget database were used to predict the transcription factors binding to the PD-L1 gene promoter region.Results PDHK inhibitors upregulated PD-L1 expression in ESCC cells in a concentration dependent manner,and within the concentration range,PDHK inhibitors had no significant effect on ESCC cell proliferation.Gene chip data and hTFtarget database predicted that PDHK inhibitors might promote PD-L1 transcriptional expression in ESCC cells through the transcription factor NFATc1.Conclusion PDHK inhibitors promote the expression of PD-L1 in esophageal squamous cell carcinoma,and the transcription factor NFATc1 may be involved in this process.