In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. LB-92-LB-92
Abstract:
Background: Patients with solid tumours are likely to have to undergo surgery during the course of their disease. Surgery and anaesthesia may influence the tumour's metastatic potential. Isoflurane is known to up-regulate hypoxia inducible factors (HIFs). HIFs are heavily implicated in tumorigenesis and may play an important role in tumour cell proliferation, migration, invasion and angiogenesis (VEGF signaling). Our aim was to investigate the potential impact of isoflurane on tumour cell progression in vitro. Methods: Human Renal Cell Carcinoma (RCC4) cells were exposed to 2% isoflurane for 2 hours at 37°C. HIF-1α, HIF-2α, p-Akt, and VEGFA protein levels were measured by Western Blotting at different time points (0, 2, 4, 8 and 24 hours) following isoflurane exposure. HIF-1α was also measured by fluorescent immunocytochemistry after cell fixation. Cell proliferation was measured by MTT and trypan blue exclusion assays. Cell migration was measured using an Oris cell migration assay. Results: Isoflurane up-regulated HIF-1α in a time-dependent manner, with the highest levels being detected at 8 hours post gas exposure (p & lt;0.001). These results were confirmed by immunofluorescence, showing a significant accumulation of HIF-1 α in the nucleus at 8 hours. Isoflurane also up-regulated HIF-2α, maximal levels were detected at 24 hours (p & lt;0.01). Isoflurane activated the PI3K pathway, as indicated by significantly raised levels of p-Akt from 4 to 24 hours, with highest levels at 8 hours (p & lt;0.001). An increase in VEGFA accumulation was seen at 24 hours (p & lt;0.01). MTT assays performed 8 hours following gas exposure demonstrated that isoflurane increased the rate of cell proliferation (p & lt;0.01), as confirmed by immunofluorescence findings at this time point. Cell migration assays showed an increased migration of Isoflurane treated cells 8 hours post exposure (p & lt;0.01), as confirmed by immunofluorescence, where an increased number of cells showing filipodia (cells migrating) was observed. Conclusion: Isoflurane at clinically relevant concentrations up-regulates HIF-1α and HIF-2α, which may be due to upstream PI3K pathway activation. Isoflurane up-regulates the major pro-angiogenic factor VEGFA and increases the rate of proliferation and migration in RCC4 cells in vitro. These findings may have major clinical implications for patients undergoing cancer surgery under general isoflurane anaesthesia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-92. doi:10.1158/1538-7445.AM2011-LB-92
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-LB-92
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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