Effect of propofol on expression of programmed death-ligand-1 in pancreatic cancer cells: the relationship with NMDA/CaMK Ⅱ/HIF-1α pathway
10.3760/cma.j.issn.0254-1416.2018.11.009
- VernacularTitle:丙泊酚对胰腺癌细胞PD-L1表达的影响:与NMDA/CaMK Ⅱ/HIF-1α通路的关系
- Author:
Juan DING
1
;
Xiangyuan CHEN
;
Yun ZHU
;
Changhong MIAO
Author Information
1. 复旦大学附属肿瘤医院麻醉科
- Keywords:
Propofol;
Pancreatic neoplasms;
Programmed death-ligand-1;
Receptors,N-methyl-D-aspartate;
Calcium-calmodulin-dependent protein kinase type 2;
Hypoxia-inducible factor 1,alpha subunit
- From:
Chinese Journal of Anesthesiology
2018;38(11):1314-1317
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effect of propofol on the expression of programmed death-ligand-1 (PD-L1) in pancreatic cancer cells and the relationship with NMDA/Ca2+/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ)/hypoxia-inducible factor-1α (HIF-1α) pathway.Methods Human pancreatic cancer cells were divided into 5 groups (n=16 each) by a simple random sampling method:control group (group C),propofol group (group P),KN93 (CaMK Ⅱ inhibitor) group,MK801 (NMDA receptor antagonist) group and propofol plus rapastinel (NMDA receptor agonist) group (group PR).Cells were cultured in DMEM supplemented with 10% fetal bovine serum in group C.Cells were incubated for 8 h with 50 μmol/L propofol in group P.Cells were incubated for 8 h with 10 μmol/L KN93 in group KN93.Cells were incubated for 8 h with 500 μmol/L MK801 in group MK801.Cells were incubated for 8 h with 50 μmol/L propofol and 20 μmol/L rapastinel in group PR.After the end of treatment in each group,the cell viability was measured using CCK8 assay,the expression of PD-L1,HIF-1α,CaMK Ⅱ and phosphorylated CaMK Ⅱ (p-CaMK Ⅱ) was detected by Western blot,and intracellular calcium concentrations were determined by Fluo3/AM probe.Results Compared with group C,the cell viability was significantly decreased,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was down-regulated,and intracellular calcium concentrations were decreased in P,KN93 and MK801 groups (P<0.05),and no significant change was found in group PR (P>0.05).Compared with group P,the cell viability was significantly enhanced,the expression of PD-L1,HIF-1α and p-CaMK Ⅱ was up-regulated,and intracellular calcium concentrations were increased in group PR (P<0.05).Conclusion The mechanism by which propofol inhibits the malignant potential of pancreatic cancer cells may be related to inhibiting NMDA/CaMK Ⅱ/HIF-1α pathway and down-regulating PD-L1 expression.