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.
Highlights
The death rate from ovarian cancer in the United States is more than double that of any other gynaecological malignancy [1, 2]
Changes induced by desflurane were different to those seen with exposure to isoflurane and sevoflurane (Figure 1), with desflurane leading to greater increases in mRNA
This analysis revealed that four of the mRNA (CXCR2, TGF-β, vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 11 (MMP11)) were significantly up-regulated and they were chosen for further investigation of protein expression
Summary
The death rate from ovarian cancer in the United States is more than double that of any other gynaecological malignancy [1, 2]. It is thought that perioperative factors may contribute to cancer recurrence [4] Surgical procedures such as biopsy and resection have been reported to disseminate cancer cells into the circulation and surrounding tissues [5] and many studies have reported that general anaesthesia dampens immune function, which is required to eliminate cancer cells [3, 6, 7]. It has been shown that, compared to general anaesthesia, epidural anaesthesia for surgery to resect colonic cancer is associated with improved survival [9]. The latest study indicated an association between certain inhalational anesthetics and ovarian cancer outcomes [10] It was reported that mortality was increased for patients with melanoma when receiving general, rather than local, anesthesia for the surgical removal of the tumour [11]. It is crucial to investigate the possible effect of anaesthetics on cancer cells
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