Cancerous phenotypes associated with hypoxia-inducible factors are not influenced by the volatile anesthetic isoflurane in renal cell carcinoma

PLoS One. 2019 Apr 15;14(4):e0215072. doi: 10.1371/journal.pone.0215072. eCollection 2019.

Abstract

The possibility that anesthesia during cancer surgery may affect cancer recurrence, metastasis, and patient prognosis has become one of the most important topics of interest in cancer treatment. For example, the volatile anesthetic isoflurane was reported in several studies to induce hypoxia-inducible factors, and thereby enhance malignant phenotypes in vitro. Indeed, these transcription factors are considered critical regulators of cancer-related hallmarks, including "sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, angiogenesis, invasion, and metastasis." This study aimed to investigate the impact of isoflurane on the growth and migration of derivatives of the renal cell line RCC4. We indicated that isoflurane treatment did not positively influence cancer cell phenotypes, and that hypoxia-inducible factors (HIFs) maintain hallmark cancer cell phenotypes including gene expressions signature, metabolism, cell proliferation and cell motility. The present results indicate that HIF activity is not influenced by the volatile anesthetic isoflurane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Isoflurane / pharmacology*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Neovascularization, Pathologic / drug therapy
  • Phenotype
  • Tumor Cells, Cultured

Substances

  • Anesthetics, Inhalation
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isoflurane

Associated data

  • figshare/10.6084/m9.figshare.6571730

Grants and funding

This work was supported by Japan Society for the Promotion of Science KAKENHI, Grants JP26670693 and JP24592336 to K.H and JP18K08874 to T.I., by a research grant from Kansai Medical University Research Consortium to K.H., by a research grant from Katano Kai to K.H., and by a grant from the National Bioscience Database Center of the Japan Science and Technology Agency to H.B.