Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2021 Mar 18;11(1):6268. doi: 10.1038/s41598-021-85241-2.
Perioperative systemic inflammation induced by surgical stress elevates the risk of hematogenous cancer metastasis. This study investigated the anti-metastatic effects and mechanisms of methylprednisolone (MP) administration for surgical stress. We examined the effects of MP on the expression of adhesion molecules in human vascular endothelial cells and in a murine hepatic metastasis model under lipopolysaccharide (LPS) administration, which mimics systemic inflammation induced by surgical stress. Serum E-selectin level was measured in blood samples obtained from 32 gastric cancer patients who were randomly assigned to treat preoperatively with or without MP. The expression of E-selectin in LPS-induced vascular endothelial cells was suppressed by MP. An adhesion assay showed the number of LPS-induced adherent tumour cells was significantly lower following MP. In the in vivo study, LPS significantly elevated the number of hepatic metastases, but pretreatment with MP before LPS significantly inhibited this elevation. The LPS-induced expression of E-selectin in the vascular endothelium of the portal vein was suppressed by MP. In human clinical samples, serum E-selectin level was significantly decreased by preoperative MP. Suppression of surgically induced systemic inflammation by MP administration might prevent hematogenous cancer metastases by suppressing the induction of E-selectin expression in the vascular endothelium.
手术应激引起的围手术期全身炎症会增加血源性癌症转移的风险。本研究探讨了甲基强的松龙（MP）用于手术应激的抗转移作用及其机制。我们检测了 MP 对脂多糖（LPS）给药下人类血管内皮细胞中黏附分子表达的影响，LPS 模拟了手术应激引起的全身炎症。从 32 名随机分配接受或不接受 MP 术前治疗的胃癌患者的血液样本中测量血清 E-选择素水平。MP 抑制 LPS 诱导的血管内皮细胞中 E-选择素的表达。黏附实验显示，在用 MP 处理后，LPS 诱导的黏附肿瘤细胞数量显著减少。在体内研究中，LPS 显著增加肝转移的数量，但 LPS 前用 MP 预处理可显著抑制这种增加。MP 抑制了 LPS 诱导的门静脉血管内皮细胞中 E-选择素的表达。在人类临床样本中，术前 MP 可显著降低血清 E-选择素水平。MP 给药抑制手术引起的全身炎症可能通过抑制血管内皮细胞中 E-选择素的诱导来防止血源性癌症转移。
