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Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α

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Abstract

Purpose

Hypoxia promotes the progression of lung cancer cells. Unfortunately, anesthetic technique might aggravate hypoxia of lung cancer cells. Sevoflurane is a commonly used anesthetic. Its effect on hypoxia-induced aggressiveness of lung cancer cells remains unknown. The aim of the study is to investigate the effects of sevoflurane on hypoxia-induced growth and metastasis of lung cancer cells. As hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in mediating the adaptation and tolerance of cancer cells under hypoxic microenvironment, the role of HIF-1α in the effect of sevoflurane on hypoxia-induced growth and metastasis has also been elucidated.

Methods

A549 cells were treated with normoxia, hypoxia, co-treatment of sevoflurane and hypoxia, and dimethyloxaloylglycine (DMOG, a HIF-1α agonist) for 4 h, respectively. MTT assay and colony formation assay were used to evaluate cell growth. Transwell assay was performed to detect invasion and migration ability. The protein level of HIF-1α, X-linked inhibitor of apoptosis protein (XIAP), survivin, fascin, heparanase (HPA), and p38 MAPK were determined by Western blotting.

Results

Hypoxia enhanced proliferation and metastatic potential of cells. Sevoflurane could suppress hypoxia-induced growth and metastasis ability of cells. Furthermore, HIF-1α, XIAP, survivin, fascin and HPA were down-regulated significantly by the co-treatment of sevoflurane and hypoxia as compared to hypoxia treatment. DMOG abolished the inhibiting effects of sevoflurane on hypoxia-induced growth and metastasis ability of cells. In addition, sevoflurane partly reversed the increase of p38 MAPK activity that was induced by hypoxia.

Conclusions

Sevoflurane could suppress hypoxia-induced growth and metastasis of lung cancer cells, which might be associated with modulating HIF-1α and its down-stream genes. Moreover, p38 MAPK signaling pathway was involved in the regulation of HIF-1α by sevoflurane.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Burfeind WR Jr, Harpole DH Jr. Surgical strategies and outcomes after induction therapy for non-small cell lung cancer. Semin Thorac Cardiovasc Surg. 2005;17:186–90.

    Article  PubMed  Google Scholar 

  3. Neeman E, Ben-Eliyahu S. Surgery and stress promote cancer metastasis: new outlooks on perioperative mediating mechanisms and immune involvement. Brain Behav Immun. 2013;30(Suppl):S32–40.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012;130:1237–50.

    Article  CAS  PubMed  Google Scholar 

  5. Demicheli R, Fornili M, Ambrogi F, Higgins K, Boyd JA, Biganzoli E, Kelsey CR. Recurrence dynamics for non-small-cell lung cancer: effect of surgery on the development of metastases. J Thorac Oncol. 2012;7:723–30.

    Article  PubMed  Google Scholar 

  6. Kuritzky AM, Ryder BA, Ng T. Long-term survival outcomes of video-assisted thoracic surgery (VATS) lobectomy after transitioning from open lobectomy. Ann Surg Oncol. 2013;20:2734–40.

    Article  PubMed  Google Scholar 

  7. Shehade H, Oldenhove G, Moser M. Hypoxia in the intestine or solid tumors: a beneficial or deleterious alarm signal? Eur J Immunol. 2014;44:2550–7.

    Article  CAS  PubMed  Google Scholar 

  8. Jian H, Liu B, Zhang J. Hypoxia and hypoxia-inducible factor 1 repress SEMA4B expression to promote non-small cell lung cancer invasion. Tumour Biol. 2014;35:4949–55.

    Article  CAS  PubMed  Google Scholar 

  9. Shaikh D, Zhou Q, Chen T, Ibe JC, Raj JU, Zhou G. cAMP-dependent protein kinase is essential for hypoxia-mediated epithelial–mesenchymal transition, migration, and invasion in lung cancer cells. Cell Signal. 2012;24:2396–406.

    Article  CAS  PubMed  Google Scholar 

  10. Brassard CL, Lohser J, Donati F, Bussieres JS. Step-by-step clinical management of one-lung ventilation: continuing professional development. Can J Anaesth. 2014;61:1103–21.

    Article  PubMed  Google Scholar 

  11. Kinsey CM, Estepar RS, Zhao Y, Yu X, Diao N, Heist RS, Wain JC, Mark EJ, Washko G, Christiani DC. Invasive adenocarcinoma of the lung is associated with the upper lung regions. Lung Cancer. 2014;84:145–50.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Liang H, Gu M, Yang C, Wang H, Wen X, Zhou Q. Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway. J Anesth. 2012;26:381–92.

    Article  PubMed  Google Scholar 

  13. Ghattass K, Assah R, El-Sabban M, Gali-Muhtasib H. Targeting hypoxia for sensitization of tumors to radio- and chemotherapy. Curr Cancer Drug Targets. 2013;13:670–85.

    Article  CAS  PubMed  Google Scholar 

  14. Shi CY, Fan Y, Liu B, Lou WH. HIF1 contributes to hypoxia-induced pancreatic cancer cells invasion via promoting QSOX1 expression. Cell Physiol Biochem. 2013;32:561–8.

    Article  CAS  PubMed  Google Scholar 

  15. Lim JH. Inhibition of the interleukin-11-STAT3 axis attenuates hypoxia-induced migration and invasion in MDA-MB-231 breast cancer cells. Korean J Physiol Pharmacol. 2014;18:391–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Zhang J, Cao J, Ma S, Dong R, Meng W, Ying M, Weng Q, Chen Z, Ma J, Fang Q, He Q, Yang B. Tumor hypoxia enhances non-small cell lung Cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling. Oncotarget. 2014;5:9664–77.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Andersen S, Eilertsen M, Donnem T, Al-Shibli K, Al-Saad S, Busund LT, Bremnes RM. Diverging prognostic impacts of hypoxic markers according to NSCLC histology. Lung Cancer. 2011;72:294–302.

    Article  PubMed  Google Scholar 

  18. Palazon A, Goldrath AW, Nizet V, Johnson RS. HIF transcription factors, inflammation, and immunity. Immunity. 2014;41:518–28.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Kumar V, Gabrilovich DI. Hypoxia-inducible factors in regulation of immune responses in tumour microenvironment. Immunology. 2014;143:512–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Po DEL, Jorge CC, Oliveira DT, Pereira MC. Hypoxic condition and prognosis in oral squamous cell carcinoma. Anticancer Res. 2014;34:605–12.

    Google Scholar 

  21. Wang Q, Hu DF, Rui Y, Jiang AB, Liu ZL, Huang LN. Prognosis value of HIF-1α expression in patients with non-small cell lung cancer. Gene. 2014;541:69–74.

    Article  CAS  PubMed  Google Scholar 

  22. Shi QY, Zhang SJ, Liu L, Chen QS, Yu LN, Zhang FJ, Yan M. Sevoflurane promotes the expansion of glioma stem cells through activation of hypoxia-inducible factors in vitro. Br J Anaesth. 2015;114:825–30.

    Article  CAS  PubMed  Google Scholar 

  23. Sun X, Fang B, Zhao X, Zhang G, Ma H. Preconditioning of mesenchymal stem cells by sevoflurane to improve their therapeutic potential. PLoS One. 2014;9:e90667.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Mimeault M, Batra SK. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells. J Cell Mol Med. 2013;17:30–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Yamada T, Horinaka M, Shinnoh M, Yoshioka T, Miki T, Sakai T. A novel HDAC inhibitor OBP-801 and a PI3 K inhibitor LY294002 synergistically induce apoptosis via the suppression of survivin and XIAP in renal cell carcinoma. Int J Oncol. 2013;43:1080–6.

    CAS  PubMed  Google Scholar 

  26. Ruckert F, Samm N, Lehner AK, Saeger HD, Grutzmann R, Pilarsky C. Simultaneous gene silencing of Bcl-2, XIAP and survivin re-sensitizes pancreatic cancer cells towards apoptosis. BMC Cancer. 2010;10:379.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Saleem M, Qadir MI, Perveen N, Ahmad B, Saleem U, Irshad T, Ahmad B. Inhibitors of apoptotic proteins: new targets for anticancer therapy. Chem Biol Drug Des. 2013;82:243–51.

    Article  CAS  PubMed  Google Scholar 

  28. 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;37:1787–804.

    Article  CAS  PubMed  Google Scholar 

  29. Chen L, Yang S, Jakoncic J, Zhang JJ, Huang XY. Migrastatin analogues target fascin to block tumour metastasis. Nature. 2010;464:1062–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Iguchi T, Aishima S, Umeda K, Sanefuji K, Fujita N, Sugimachi K, Gion T, Taketomi A, Maehara Y, Tsuneyoshi M. Fascin expression in progression and prognosis of hepatocellular carcinoma. J Surg Oncol. 2009;100:575–9.

    Article  PubMed  Google Scholar 

  31. Nagatsuka H, Han PP, Tsujigiwa H, Siar CH, Gunduz M, Sugahara T, Sasaki A, Nakajima M, Naomoto Y, Nagai N. Heparanase gene and protein expression in ameloblastoma: possible role in local invasion of tumor cells. Oral Oncol. 2005;41:542–8.

    Article  CAS  PubMed  Google Scholar 

  32. Ma XM, Shen ZH, Liu ZY, Wang F, Hai L, Gao LT, Wang HS. Heparanase promotes human gastric cancer cells migration and invasion by increasing Src and p38 phosphorylation expression. Int J Clin Exp Pathol. 2014;7:5609–21.

    PubMed Central  PubMed  Google Scholar 

  33. Zhu T, Zhan L, Liang D, Hu J, Lu Z, Zhu X, Sun W, Liu L, Xu E. Hypoxia-inducible factor 1α mediates neuroprotection of hypoxic postconditioning against global cerebral ischemia. J Neuropathol Exp Neurol. 2014;73:975–86.

    Article  CAS  PubMed  Google Scholar 

  34. Emerling BM, Platanias LC, Black E, Nebreda AR, Davis RJ, Chandel NS. Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling. Mol Cell Biol. 2005;25:4853–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Lin Y, Liu A, Lu N, Li Y, Song Q, Yu H, Li X. Inhibitive effects of low oxygen and glucose deprivation on brain-pancreas relative protein expression via hypoxia-inducible factor-1 pathways. Cell Physiol Biochem. 2008;22:353–62.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by Guangdong Province Medicine Scientific Research Fund, Guangdong province, China (B2013372).

Conflict of interest

The authors declare that they have no conflicts of interest concerning this article.

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Authors and Affiliations

  1. Department of Anesthesiology, Affiliated FoShan Hospital of SUN YAT-SEN University, 528000, Foshan, China

    Hua Liang, Cheng Xiang Yang, Bin Zhang, Han Bing Wang, Hong Zhen Liu, Xiao Hong Lai, Mei Juan Liao & Tao Zhang

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  1. Hua Liang
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  2. Cheng Xiang Yang
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  3. Bin Zhang
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Correspondence to Hua Liang.

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Liang, H., Yang, C.X., Zhang, B. et al. Sevoflurane suppresses hypoxia-induced growth and metastasis of lung cancer cells via inhibiting hypoxia-inducible factor-1α. J Anesth 29, 821–830 (2015). https://doi.org/10.1007/s00540-015-2035-7

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  • DOI: https://doi.org/10.1007/s00540-015-2035-7

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