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

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Abstract

Background

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.

Materials and methods

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.

Results

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).

Conclusions

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.

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Acknowledgements

The authors will thank Dr. Hai Jiang for his great help in pre-experiment execution. This work was supported by the National Natural Science Foundation of China (Grant numbers 30972857, 2010 and 81672405, 2016). The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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Author notes

  1. Zegeng Su, Pinbo Huang and Xijiu Ye contributed equally to this work.

  2. Jie Wang and Ruixia Chen co-corresponding author.

Authors and Affiliations

  1. Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 West Yan Jiang Road, 510120, Guangzhou, People’s Republic of China

    Zegeng Su, Xijiu Ye, Weixing Li & Ruixia Chen

  2. Department of Anesthesiology, Jieyang People’s Hospital, Jieyang, People’s Republic of China

    Zegeng Su

  3. Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

    Pinbo Huang, Yongcong Yan, Kang Xu & Jie Wang

  4. Department of Neurosurgery, Shantou Central Hospital, Shantou, People’s Republic of China

    Shuaibin Huang

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  1. Zegeng Su
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Su, Z., Huang, P., Ye, X. et al. Ropivacaine via nuclear factor kappa B signalling modulates CD62E expression and diminishes tumour cell arrest. J Anesth 33, 685–693 (2019). https://doi.org/10.1007/s00540-019-02699-1

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  • DOI: https://doi.org/10.1007/s00540-019-02699-1

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