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      Sevoflurane Inhibited Osteosarcoma Cell Proliferation And Invasion Via Targeting miR-203/WNT2B/Wnt/β-Catenin Axis

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          Abstract

          Background

          Osteosarcoma is one of the most common primary bone cancers with predominant occurrence in children and adolescents. This study aimed to determine the effects of sevoflurane treatment on the osteosarcoma progression and to explore the underlying molecular mechanisms.

          Materials and methods

          The mRNA and protein expression levels were determined by qPCR and Western blot, respectively. Osteosarcoma cell proliferation, apoptosis and invasion were determined by MTT, caspase-3 activity, colony formation and Transwell invasion assays, respectively. The interaction between miR-203 and WNT2B 3ʹ untranslated region was confirmed by luciferase reporter assay.

          Results

          Sevoflurane treatment for 6 hrs concentration-dependently suppressed cell viability, increased caspase-3 activity and up-regulated miR-203 expression in both U2OS and MG63 cells. MiR-203 overexpression suppressed cell viability, increased caspase-3 activity and suppressed cell growth and invasion of osteosarcoma cells. In addition, miR-203 knockdown attenuated the tumor-suppressive effects of sevoflurane treatment on osteosarcoma cells. Mechanistic studies showed that miR-203 repressed the expression of WNT2B in U2OS cells, and inhibition of miR-203 attenuated the suppressive effects of sevoflurane on WNT2B expression. More importantly, WNT2B overexpression attenuated the effects of sevoflurane treatment on cell viability, caspase-3 activity, cell growth and invasion of U2OS cells. MiR-203 overexpression suppressed Wnt/β-catenin signalling. Similarly, sevoflurane suppressed the activity of Wnt/β-catenin signalling, which was partially reversed by miR-203 knockdown and WTN2B overexpression.

          Conclusion

          Our data showed the tumor-suppressive effects of sevoflurane on osteosarcoma cells, and mechanistic studies revealed that sevoflurane inhibited osteosarcoma cell proliferation and invasion partly via targeting the miR-203/WNT2B/Wnt/β-catenin axis.

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          Most cited references22

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          Outcomes of cancer surgery after inhalational and intravenous anesthesia: A systematic review

          Sinor Soltanizadeh, Thea H. Degett, Ismail Gögenur (2017)
          Perioperative factors are probably essential for different oncological outcomes. This systematic review investigates the literature concerning overall mortality and postoperative complications after cancer surgery with inhalational (INHA) and intravenous anesthesia (TIVA). A search was conducted according to the PRISMA guidelines, including studies with patients undergoing surgery for cancer and where TIVA was compared with INHA. Two investigators identified relevant papers in the databases: PubMed, Scopus, EMBASE and the Cochrane Library. Risks of bias assessment tools from the Cochrane Collaboration were used for evaluating quality of evidence. Eight studies with a total of 10,696 patients were included. Four studies reported data regarding overall mortality and four studies reported data regarding postoperative complications. Evidence was evaluated to be of moderate to serious risk of bias. Three retrospective studies presented a hazard ratio (HR) adjusting for several confounders. One study reported an increased overall mortality after INHA with a HR of 1.47 (95% CI 1.31-1.64, p≤0.001), while another study reported a tendency of decreased overall mortality after TIVA (HR 0.85, 95% CI 0.72-1.00, p=0.051). A third study showed no difference in the overall mortality, but prolonged recurrence-free survival after TIVA with a HR of 0.48 (95% CI 0.27-0.86, p=0.014). In one study, the rate of pulmonary complications was significantly higher after INHA compared with TIVA, while other postoperative complications were comparable. There are currently four propensity-adjusted retrospective studies indicating that TIVA might be the preferred anesthetic choice in cancer surgery. However, evidence is currently of low quality and randomized clinical trials are required for further investigation.
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            Sevoflurane inhibits the migration and invasion of colorectal cancer cells through regulating ERK/MMP-9 pathway by up-regulating miR-203

            Lihua Fan, Yini Wu, Jianping Wang … (2019)
            Article 0 comments Cited 41 times – based on 0 reviews     Review now
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              Implicating anaesthesia and the perioperative period in cancer recurrence and metastasis

              Julia Dubowitz, Erica K. Sloan, Bernhard Riedel (2018)
              Article 0 comments Cited 39 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): CMAR
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 11 November 2019
                Publication date Collection: 2019
                Volume: 11
                Pages: 9505-9515
                Affiliations
                [1 ]Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou, People’s Republic of China
                [2 ]Department of Andrology, The Seventh Affiliated Hospital, Sun Yat-Sen University , Guangzhou, People’s Republic of China
                Author notes
                Correspondence: Fuding Lu Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou, People’s Republic of ChinaTel +86-13560371081 Email lfd19870901@126.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 225911
                DOI: 10.2147/CMAR.S225911
                PMC ID: 6858624
                PubMed ID: 31814757
                SO-VID: 72c8259e-f0ff-4f93-998f-5518902b12ab
                Copyright © © 2019 Chen et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 03 August 2019
                Date accepted : 15 October 2019
                Page count
                Figures: 6, References: 30, Pages: 11
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: osteosarcoma,proliferation,invasion,sevoflurane,mir-203,wnt2b,wnt/β-catenin
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: osteosarcoma, proliferation, invasion, sevoflurane, mir-203, wnt2b, wnt/β-catenin

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