Volatile anaesthetics enhance the metastasis related cellular signalling including CXCR2 of ovarian cancer cells

Abstract

The majority of ovarian cancer patients relapse after surgical resection. Evidence is accumulating regarding the role of surgery in disseminating cancer cells; in particular anaesthesia may have an impact on cancer re-occurrence. Here, we have investigated the metastatic potential of volatile anaesthetics isoflurane, sevoflurane and desflurane on ovarian cancer cells.Human ovarian carcinoma cells (SKOV3) were exposed to isoflurane (2%), sevoflurane (3.6%) or desflurane (10.3%) for 2 hours. Metastatic related gene expression profiles were measured using the Tumour Metastasis PCR Array and qRT-PCR. Subsequently vascular endothelial growth factor A (VEGF-A), matrix metalloproteinase 11 (MMP11), transforming growth factor beta-1 (TGF-β1) and chemokine (C-X-C motif) receptor 2 (CXCR2) proteins expression were determined using immunofluorescent staining. The migratory capacities of SK-OV3 cells were assessed with a scratch assay and the potential role of CXCR2 in mediating the effects of volatile anaesthetics on cancer cell biology were further investigated with CXCR2 knockdown by siRNA.All three volatile anaesthetics altered expression of 70 out of 81 metastasic related genes with significant increases in VEGF-A, MMP-11, CXCR2 and TGF-β genes and protein expression with a magnitude order of desflurane (greatest), sevoflurane and isoflurane. Scratch analysis revealed that exposure to these anesthetics increased migration, which was abolished by CXCR2 knockdown.Volatile anaesthetics at clinically relevant concentrations have strong effects on cancer cell biology which in turn could enhance ovarian cancer metastatic potential. This work raises the urgency for further in vivo studies and clinical trials before any conclusions can be made in term of the alteration of clinical practice.

Differential effects of calcium on PI3K-Akt and HIF-1α survival pathways

“…Data are the mean ± SEM of at least three independent experiments. *P < 0.05, **P < 0.01, and † P < 0.001 compared with control between these two proteins was detected even under specific stressful conditions, i.e., in the presence of the carcinogenic benzo[α]pyrene (Mavrofrydi and Papazafiri 2012) or volatile anesthetics (Benzonana et al 2013;Huang et al 2014;Iwasaki et al 2016). Here, we present evidence of a crosstalk between pAkt and HIF-1α during calcium homeostasis disturbances.…”

Propofol Disrupts Aerobic Glycolysis in Colorectal Cancer Cells via Inactivation of the NMDAR-CAMKII-ERK Pathway

“…Moreover, investigations on intravenous anesthetics have discovered that propofol has an opposite effect to inhaled anesthetics, i.e., suppressing metastasis and promoting apoptosis of tumor cells [30, 33-35]. A recent study found that propofol inhibited the activation of NMDAR, a Ca 2+ channel [36].…”

Propofol Attenuates Lung but not Brain Cancer Cell Malignancy through Metabolism and Cell Signaling Modulation&nbsp;In Vitro

“…However, the mechanisms underlying these clinical observations remain unknown. A previous study demonstrated volatile anesthetics, such as, sevoflurane, isoflurane, and desflurane, upregulated the metastatic genes in ovarian cancer cells (10). Furthermore, unlike propofol, isoflurane was also demonstrated to increase hypoxia-inducible factor-1 alpha (HIF-1α) (11), which is a transcriptional activator associated with the progression of a variety of cancer types, such as breast, colon, and lung cancer (12).…”