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.
Highlights
The hypothesis that anesthesia during cancer surgery may affect tumor recurrence, metastasis, and patient prognosis [1, 2] is gaining currently increasing importance [3]
hypoxia-inducible transcription factors (HIFs)-1α and HIF-2α protein were detected at 20% O2 in RCC4-EV cells, but not in RCC4-von Hippel-Lindau (VHL) cells (Fig 1A, S1 Fig)
To investigate possible protocol-dependent effects, HIF-1α was quantified in RCC4-EV and RCC4-VHL cells exposed to isoflurane for 2 h and incubated for 6 h at either 20% or 1% O2 (Fig 1D)
Summary
The hypothesis that anesthesia during cancer surgery may affect tumor recurrence, metastasis, and patient prognosis [1, 2] is gaining currently increasing importance [3]. Numerous recent in vitro, in vivo, retrospective, and translational studies have investigated the effect of anesthetics on perioperative immunity and cancer metastatic potential. Isoflurane was reported in several studies to induce hypoxia-inducible transcription factors (HIFs), and thereby enhance malignant phenotypes in vitro [4,5,6]. HIF-1 was originally cloned as a driver of erythropoietin expression [7,8,9,10]; shortly thereafter, it was reportedly associated with the tumor grade in various cancers [11].
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