中国医科大学学报2024，Vol.53Issue(5)：414-420,7.DOI:10.12007/j.issn.0258-4646.2024.05.005
延胡索通过靶向CXCL17激活AMPK信号通路下调PD-L1抑制EB病毒感染诱导的胃癌免疫逃逸
Rhizoma corydalis downregulates PD-L1 by targeting CXCL17 to activate AMPK signaling pathway and inhibits EBV-induced immune escape in gastric cancer
摘要
Abstract
Objective To explore the effect of Rhizoma corydalis on the immune escape of Epstein-Barr virus(EBV)positive gastric cancer cells and its mechanism of targeting CXCL17 to affect immune escape of EBV-positive gastric cancer cells.Methods GEO2R online analysis software was used to screen differentially expressed genes in EBV-positive gastric cancer tissues.EBV-negative AGS gastric cancer cells and EBV-positive SUN-719 gastric cancer cells were used for the experiments.RT-qPCR and Western blotting were used to detect the expression of CXCL17in EBV-negative and EBV-positive gastric cancer cells.Transfection of CXCL17 siRNA into EBV-positive gastric cancer cells,detection of PD-L1 expression through Western blotting,coculture of EBV-positive gastric cancer cells with T cells,detection of cell viability using the CCK-8 assay,and detection of cell apoptosis rate through flow cytometry were conducted.EBV-positive gastric cancer cells were treated with different concentrations of a Rhizoma corydalis extract(2,4,and 8 μg/mL).The expression of CXCL17and PD-L1 was detected through Western blotting,and EBV-positive gastric cancer cells were cocultured with T cells.Cell viability was determined using CCK-8,and cell apoptosis rate through flow cytometry.The CXCL17overexpression plasmid was transfected into EBV-positive gastric cancer cells treated with Rhizoma corydalis extract(8μg/mL).The expression of PD-L1 and p-AMPK was detected through Western blotting,and EBV-positive gastric cancer cells were cocultured with T cells.Cell viability was determined using CCK-8,and cell apoptosis rate with flow cytometry.Results CXCL17 expression was upregulated in EBV-positive gastric cancer tissues and cells(P<0.05).Silencing of CXCL17reduced the expression of PD-L1 in EBV-positive gastric cancer cells,inhibited the proliferation of EBV-positive gastric cancer cells cocultured with T cells,and promoted cell apoptosis(P<0.05).Rhizoma corydalis treat-ment reduced the expression of CXCL17 and PD-L1 in EBV-positive gastric cancer cells,inhibited the proliferation of EBV-positive gas-tric cancer cells cocultured with T cells,and promoted apoptosis(P<0.05).Overexpression of CXCL17reversed the inhibitory effect of the Rhizoma corydalis treatment on PD-L1 expression and cell proliferation in EBV-positive gastric cancer cells,as well as the promoting effect of cell apoptosis(P<0.05).Overexpression of CXCL17also reduced the expression of p-AMPK in EBV-positive gastric cancer cells treated with Rhizoma corydalis(P<0.05).Conclusion CXCL17 expression is upregulated in EBV-positive gastric cancer cells,and Rhizoma corydalis inhibits immune escape in gastric cancer cells by downregulating CXCL17 expression in EBV-positive gastric cancer cells,which may be related to the activation of the AMPK signaling pathway.关键词
延胡索/胃癌/EB病毒/免疫逃逸/CXCL17/AMPK信号通路Key words
Rhizoma corydalis/gastric cancer/Epstein-Barr virus/immune escape/CXCL17/AMPK signaling pathway分类
医药卫生引用本文复制引用
韩超,胡晓云,刘畅,于洋洋..延胡索通过靶向CXCL17激活AMPK信号通路下调PD-L1抑制EB病毒感染诱导的胃癌免疫逃逸[J].中国医科大学学报,2024,53(5):414-420,7.基金项目
辽宁省自然科学基金(2022-BS-121) （2022-BS-121）
