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Journal of Anesthesia

Published in:

01-06-2012 | Original Article

Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway

Authors: Hua Liang, Miaoning Gu, Chengxiang Yang, Hanbing Wang, Xianjie Wen, Qiaoling Zhou

Published in: Journal of Anesthesia | Issue 3/2012

Abstract

Purpose

Sevoflurane is used widely during lung cancer surgery. However, the effect of sevoflurane on the invasion and migration of lung carcinoma cells remains unclear. The aims of this study were to explore the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the effect of sevofluane on the invasion and the role of fascin and ezrin on the effect of sevofluane on the migration of human lung adenocarcinoma A549 cells. We also investigated whether sevoflurane regulates the expression of these molecules through the p38 mitogen-activated protein kinase (MAPK) signaling pathway.

Methods

The invasion of cells was evaluated using the Transwell invasion assay, and the migration of cells was determined using the wound healing assay. The expression of MMP-2, MMP-9, ezrin, fascin, and phospho-p38 MAPK in cells was determined by western blotting.

Results

A significant inhibition of cell invasion and migration was found in A549 cells which had been treated with sevoflurane. The data also revealed that sevoflurane could decrease the phosphorylation level of p38 MAPK, which is involved in the downregulation of MMP-2, MMP-9, fascin, and ezrin expression, accompanied by a concomitant inhibition of the invasion and migration of A549 cells. SB203580, a p38 MAPK inhibitor, augmented the downregulation of the expression of these proteins.

Conclusion

The anti-invasion effect of sevoflurane on A549 cells was associated with a downregulation of both MMP-2 and MMP-9 expression, while the anti-migration effect was associated with a downregulation of both fascin and ezrin expression. These effects could occur partly as a result of inactivation of the p38 MAPK signaling pathway.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRef

Ludwig C, Stoelben C, Olschewski M, Hasse J. Comparison of morbidity, 30-day mortality, and long-term survival after pneumonectomy and sleeve lobectomy for non-small cell lung carcinoma. Ann Thorac Surg. 2005;79:968–73.PubMedCrossRef

Rueth NM, Parsons HM, Habermann EB, Groth SS, Virnig BA, Tuttle TM, Andrade RS, Maddaus MA, D’cunha J. The long-term impact of surgical complications after resection of stage I non-small cell lung cancer: a population-based survival analysis. Ann Surg. 2011;254:368–74.PubMedCrossRef

Friedl P, Wolf K. Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 2003;3:362–74.PubMedCrossRef

Snyder GL, Greenberg S. Effect of anaesthetic technique and other perioperative factors on cancer recurrence. Br J Anaesth. 2010;105:106–15.PubMedCrossRef

Gottschalk A, Sharma S, Ford J, Durieux ME, Tiouririne M. Review article: the role of the perioperative period in recurrence after cancer surgery. Anesth Analg. 2010;110:1636–43.PubMedCrossRef

Kvolik S, Glavas-Obrovac L, Bares V, Karner I. Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines. Life Sci. 2005;77:2369–83.PubMedCrossRef

Kvolik S, Dobrosevic B, Marczi S, Prlic L, Glavas-Obrovac L. Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia. Acta Anaesthesiol Scand. 2009;53:1192–9.PubMedCrossRef

Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141:52–67.PubMedCrossRef

10.

Hashimoto Y, Skacel M, Adams JC. Roles of fascin in human carcinoma motility and signaling: Prospects for a novel biomarker? Int J Biochem Cell Biol. 2005;7:1787–804.CrossRef

11.

Hunter KW. Ezrin, a key component in tumor metastasis. Trends Mol Med. 2004;10:201–4.PubMedCrossRef

12.

Mao L, Yuan L, Slakey LM, Jones FE, Burow ME, Hill SM. Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway. Breast Cancer Res. 2010;12:R107.PubMedCrossRef

13.

Wynne S, Djakiew D. NSAID inhibition of prostate cancer cell migration is mediated by Nag-1 Induction via the p38 MAPK-p75(NTR) pathway. Mol Cancer Res. 2010;8:1656–64.PubMedCrossRef

14.

Loop T, Scheiermann P, Doviakue D, Musshoff F, Humar M, Roesslein M, Hoetzel A, Schmidt R, Madea B, Geiger KK, Pahl HL, Pannen BH. Sevoflurane inhibits phorbol-myristate-acetate-induced activator protein-1 activation in human T lymphocytes in vitro: potential role of the p38-stress kinase pathway. Anesthesiology. 2004;101:710–21.PubMedCrossRef

15.

Roesslein M, Frick M, Auwaerter V, Humar M, Goebel U, Schwer C, Geiger KK, Pahl HL, Pannen BH, Loop T. Sevoflurane-mediated activation of p38-mitogen-activated stressskinase is independent of apoptosis in Jurkat T-cells. Anesth Analg. 2008;106:1150–60.PubMedCrossRef

16.

Coffey JC, Wang JH, Smith MJ, Bouchier-Hayes D, Cotter TG, Redmond HP. Excisional surgery for cancer cure: therapy at a cost. Lancet Oncol. 2003;4:760–8.PubMedCrossRef

17.

Yamaguchi K, Takagi Y, Aoki S, Futamura M, Saji S. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg. 2000;232:58–65.PubMedCrossRef

18.

Chetty C, Rao JS, Lakka SS. Matrix metalloproteinase pharmacogenomics in non-small-cell lung carcinoma. Pharmacogenomics. 2011;12:535–46.PubMedCrossRef

19.

Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002;295:2387–92.PubMedCrossRef

20.

Iniesta P, Morán A, De Juan C, Gómez A, Hernando F, García-Aranda C, Frías C, Díaz-López A, Rodríguez-Jiménez FJ, Balibrea JL, Benito M. Biological and clinical significance of MMP-2, MMP-9, TIMP-1 and TIMP-2 in non-small cell lung cancer. Oncol Rep. 2007;17:217–23.PubMed

21.

Jayo A, Parsons M. Fascin: a key regulator of cytoskeletal dynamics. Int J Biochem Cell Biol. 2010;42(10):1614–7.PubMedCrossRef

22.

Yoder BJ, Tso E, Skacel M, Pettay J, Tarr S, Budd T, Tubbs RR, Adams JC, Hicks DG. The expression of fascin, an actin-bundling motility protein, correlates with hormone receptor-negative breast cancer and a more aggressive clinical course. Clin Cancer Res. 2005;11:186–92.PubMed

23.

Hashimoto Y, Skacel M, Lavery IC, Mukherjee AL, Casey G, Adams JC. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas. BMC Cancer. 2006;6:241.PubMedCrossRef

24.

Li Q, Wu M, Wang H, Xu G, Zhu T, Zhang Y, Liu P, Song A, Gang C, Han Z, Zhou J, Meng L, Lu Y, Wang S, Ma D. Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells. Cancer Lett. 2008;261:55–63.PubMedCrossRef

25.

Ma L, Liu YP, Geng CZ, Xing LX, Zhang XH. Low-dose epirubicin inhibits ezrin-mediated metastatic behavior of breast cancer cells. Tumori. 2011;97:400–5.PubMed

26.

Bruce B, Khanna G, Ren L, Landberg G, Jirström K, Powell C, Borczuk A, Keller ET, Wojno KJ, Meltzer P, Baird K, McClatchey A, Bretscher A, Hewitt SM, Khanna C. Expression of the cytoskeleton linker protein ezrin in human cancers. Clin Exp Metastasis. 2007;24:69–78.PubMedCrossRef

27.

Wagner EF. Nebreda AR.Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 2009;9:537–49.PubMedCrossRef

28.

Cuenda A, Rousseau S. p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta. 2007;1773:1358–75.PubMedCrossRef

29.

Dhanasekaran DN, Johnson GL. MAPKs: function, regulation, role in cancer and therapeutic targeting. Oncogene. 2007;26:3097–9.PubMedCrossRef

Title: Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway
Authors: Hua Liang
Miaoning Gu
Chengxiang Yang
Hanbing Wang
Xianjie Wen
Qiaoling Zhou
Publication date: 01-06-2012
Publisher: Springer Japan
Published in: Journal of Anesthesia / Issue 3/2012
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-011-1317-y

At a glance: The STEP trials

Springer Medicine

Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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