Abstract
(1) Background: Triple negative breast cancer (TNBC) is a highly aggressive tumor, associated with high rates of early distant recurrence and short survival times, and treatment may require surgery, and thus anesthesia. The effects of anesthetic drugs on cancer progression are under scrutiny, but published data are controversial, and the involved mechanisms unclear. Anesthetic agents have been shown to modulate several molecular cascades, including PI3K/AKT/mTOR. AKT isoforms are frequently amplified in various malignant tumors and associated with malignant cell survival, proliferation and invasion. Their activation is often observed in human cancers and is associated with decreased survival rate. Certain anesthetics are known to affect hypoxia cell signaling mechanisms by upregulating hypoxia-inducible factors (HIFs). (2) Methods: MCF-10A and MDA-MB 231 cells were cultivated and CellTiter-Blue® Cell Viability assay, 2D and 3D matrigel assay, immunofluorescence assays and gene expressions assay were performed after exposure to different sevoflurane concentrations. (3) Results: Sevoflurane exposure of TNBC cells results in morphological and behavioral changes. Sevoflurane differently influences the AKT isoforms expression in a time-dependent manner, with an important early AKT3 upregulation. The most significant effects occur at 72 h after 2 mM sevoflurane treatment and consist in increased viability, proliferation and aggressiveness and increased vimentin and HIF expression. (4) Conclusions: Sevoflurane exposure during surgery may contribute to cancer recurrence via AKT3 induced epithelial–mesenchymal transition (EMT) and by all three AKT isoforms enhanced cancer cell survival and proliferation.
Highlights
IntroductionBoth biological and therapy-related, influence cancer evolution and progression
Multiple factors, both biological and therapy-related, influence cancer evolution and progression
In human breast adenocarcinoma cell line (MDA-MB-231) viability was dynamic, significantly decreasing 24 h post sevoflurane exposure (Figure 1B) and significantly increasing at 72 h post sevoflurane treatment (Figure 1C), results observed at all concentrations
Summary
Both biological and therapy-related, influence cancer evolution and progression. A complex process that requires release of metastatic cells from a primary tumor, invasion and (local, lymphatic, intravascular) migration and subsequent extravasation and proliferation in target tissues, is accounted for 90% of cancer death [1,2,3]. Cellular and molecular events associated with the metastatic process may be significantly influenced by many factors during and immediately after surgery [4,5]. Various studies suggest that the choice of anesthesia technique/drugs could affect longterm outcome after surgery [6,7,8]. Deegan et al demonstrated that serum of patients with breast cancer surgery, taking place under two different anesthesia techniques, induce different effects on cancer cell proliferation and migration, differently influencing
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