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-1a (HIF-1a) 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-1a 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-1a neosynthesis through
upper pathway blocking by a PI-3K-Akt inhibitor or HIF-1a siRNA abolished isoflurane-induced effects. In contrast, the intravenous
anaesthetic propofol inhibited HIF-1a activation induced by hypoxia or CoCl2. Propofol also prevented isoflurane-induced HIF-1a
activation, and partially reduced cancer cell malignant activities.
Conclusions: Our findings suggest that modulation of HIF-1a 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.