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Br J Cancer. 2014 Sep 23;111(7):1338-49. doi: 10.1038/bjc.2014.426. Epub 2014 Jul 29.

Prostate cancer cell malignancy via modulation of HIF-1α pathway with isoflurane and propofol alone and in combination.

Author information

1
1] Section of Anaesthetics, Pain Medicine and Intensive Care, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK [2] Department of Anesthesiology, West China Second Hospital, Sichuan University, Chengdu, China.
2
Section of Anaesthetics, Pain Medicine and Intensive Care, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
3
Division of Cancer, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK.

Abstract

BACKGROUND:

Surgery is considered to be the first line treatment for solid tumours. Recently, retrospective studies reported that general anaesthesia was associated with worse long-term cancer-free survival when compared with regional anaesthesia. This has important clinical implications; however, the mechanisms underlying those observations remain unclear. We aim to investigate the effect of anaesthetics isoflurane and propofol on prostate cancer malignancy.

METHODS:

Prostate cancer (PC3) cell line was exposed to commonly used anaesthetic isoflurane and propofol. Malignant potential was assessed through evaluation of expression level of hypoxia-inducible factor-1α (HIF-1α) and its downstream effectors, cell proliferation and migration as well as development of chemoresistance.

RESULTS:

We demonstrated that isoflurane, at a clinically relevant concentration induced upregulation of HIF-1α and its downstream effectors in PC3 cell line. Consequently, cancer cell characteristics associated with malignancy were enhanced, with an increase of proliferation and migration, as well as development of chemoresistance. Inhibition of HIF-1α neosynthesis through upper pathway blocking by a PI-3K-Akt inhibitor or HIF-1α siRNA abolished isoflurane-induced effects. In contrast, the intravenous anaesthetic propofol inhibited HIF-1α activation induced by hypoxia or CoCl2. Propofol also prevented isoflurane-induced HIF-1α activation, and partially reduced cancer cell malignant activities.

CONCLUSIONS:

Our findings suggest that modulation of HIF-1α activity by anaesthetics may affect cancer recurrence following surgery. If our data were to be extrapolated to the clinical setting, isoflurane but not propofol should be avoided for use in cancer surgery. Further work involving in vivo models and clinical trials is urgently needed to determine the optimal anaesthetic regimen for cancer patients.

PMID:
25072260
PMCID:
PMC4183852
DOI:
10.1038/bjc.2014.426
[Indexed for MEDLINE]
Free PMC Article

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