Effect of Preoperative Administration of Methylpredonisolone and Ulinastatin on Tumor Cell Metastasis after Surgical Stress

Abstract

Using a rat laparotomy stress model, we conducted a comparative analysis of postoperative organ metastasis after administration of ulinastatin (UTI) or methylprednisolone (MP), which have an inhibitory effect on cytokine production. The subjects were classified into 4 groups: 1) minimal laparotomy group (C group), 2) major laparotomy group (L group), 3) preoperative MP intravenous administration + major laparotomy group (MP group), and 4) preoperative UTI intravenous administration + major laparotomy group (UTI group). Either MP or UTI was administered intravenously before surgery, and RI-labeled cells were injected into the portal vein immediately after laparotomy to collect tissue specimens in order to measure radiation dosage. Then, the concentrations of serum IL-2 and IL-6, liver interleukin 1 beta (IL-1β) and interleukin 10 (IL-10), and liver E-selectin were measured. In addition natural killer cell, (NK cell) activation and neoplastic nodules on the liver surface at 3 weeks after surgery were also measured. The adhesion rate of malignant cells to the liver was higher in the L group than in the C group, higher in the MP group than the L group, and lower overall in the UTI group. The concentration of IL-1β and IL-6 were decreased in the MP and UTI groups compared to the L group. IL-2 was decreased significantly in the MP group compared with the C and L groups. E-selectin expression level decreased in the UTI group compared with the L group. NK cell activation decreased in the MP group compared with the C group and L group, but no differences were observed between the UTI and L groups. The number of tumor nodules on the surface of the liver increased in the MP group compared with the L group, and decreased in the UTI group compared with the L group. Postoperative alleviation of invasive reaction was suggested in both the MP and UTI groups. However, preoperative administration of MP increased metastasis while that of UTI inhibited metastasis. MP was considered to have decreased anti-tumor immunocompetence and promoted metastasis, while UTI was considered to have inhibited the expression of adhesive molecules and decreased metastasis.

Effect of ulinastatin on the inflammatory response after video-assisted thoracic lobectomy in patients with lung cancer: a randomized controlled study

“…[9][10][11][12] Various studies have demonstrated a protective effect of UTI in the immune response and cancer metastasis. [32][33][34][35][36] They reported that UTI reduced cancer metastasis by inhibiting cancer adhesive molecules, inhibiting expression of phospho-extracellular signalregulated kinase gene, or its anti-plasmin activity.…”

“…In addition, UTI exerts an anti-metastatic effect by inhibiting the expression of urokinase-type plasminogen activator and inhibiting the cell-binding plasmin and cathepsin B activities involved in tumor cell proliferation and progression [9–12] . Various studies have demonstrated a protective effect of UTI in the immune response and cancer metastasis [32–36] . They reported that UTI reduced cancer metastasis by inhibiting cancer adhesive molecules, inhibiting expression of phospho-extracellular signalregulated kinase gene, or its anti-plasmin activity.…”

Protective effects of ulinastatin and methylprednisolone against radiation-induced lung injury in mice

“…[ 16 ] reported that methylprednisolone combined with bone marrow mesenchymal stem cells can inhibit paraquat-induced acute lung injury. The combined use of methylprednisolone and ulinastatin has a major effect on tumor cell metastasis after surgical stress and experimental autoimmune encephalomyelitis [ 17 , 18 ]. However, there has been no report concerning combined therapy with ulinastatin and methylprednisolone in RILI.…”

Long-Term Outcomes after Use of Perioperative Glucocorticoids in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analysis

“…The available evidence remains heterogenous; low in quality and amount; and cancer-specific at present.Cancers 2020, 12, 76 2 of 22 such as glucocorticoids. Preliminary animal studies have investigated the effect of steroids on cancer progression and the results are not conclusive [6,7]. Some suggest that endogenous glucocorticoids released from prolonged stress response may hinder natural killer (NK) cell activity, which is essential in malignant defence, but the effect might not be as significant as the NK cell suppression mediated by stress related catecholamines [8].…”