Ropivacaine via nuclear factor kappa B signalling modulates CD62E expression and diminishes tumour cell arrest

The issue whether anaesthesia has an impact on the prognosis of carcinoma has been widely discussed and remains debated. Ropivacaine has been widely used in perioperative period as a long acting local anesthetic. An early event during recurrence or metastasis of carcinoma is the adhesion of circulating tumour cells (CTCs) to endothelial cells (ECs) through binding adhesion molecules that are up-regulated on inflamed endothelium during the perioperative period or other periods. This study was to explore the impact of ropivacaine on the adhesion of tumour cells, providing evidences of its influence on the prognosis of carcinoma.

Human umbilical vein endothelial cells (HUVECs) were pre-treated with ropivacaine (10^-7-10^-5 M; 30 min) prior to treatment with tumour necrosis factor alpha (TNFα) (10 ng ml^-1; 1, 4 and 8 h). Intercellular adhesion molecule-1 (ICAM-1), endothelial-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1) mRNA levels were detected via quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). To clarify the underlying action mechanism, p65, p-p65, IκBα, p-IκBα, IKKα/β and p-IKKα/β protein levels were evaluated via western blotting. Cell viability and tumour cell adhesion assays were also assessed.

The clinically usage concentration of ropivacaine (10^-6 M) produced a significant decrease in CD62E expression compared with that produced by TNFα only (p < 0.001). Moreover, adhesion assays showed that ropivacaine effectively inhibited the adhesion of hepatoma cells (p < 0.01), human colon cancer cells (p < 0.01) and human leukemic monocyte (p < 0.01). Western blot results showed that pre-treatment with ropivacaine inhibited the phosphorylation of p65 (p < 0.05), IκBα (p < 0.001) and IKKα/β (p < 0.01).

Ropivacaine decreased the adhesion of tumour cells. Ropivacaine modulated CD62E expression by inhibiting the activation of NF-κB. These results might provide new insight into the issue whether anaesthesia has an impact on the prognosis of carcinoma.