Effects of different sevoflurane concentrations on Akt isoforms in normal and cancer breast cells. An experimental model

Abstract

Introduction: Multiple perioperative factors influence cancer patient evolution and outcome. Microenvironmental factors activate different gene programs that enable tumor cell to invade, survive and promote drug resistance and metastasis. The effects of anesthetic drugs on cancer progression is under scrutiny, but published data are controversial and the involved mechanisms unclear. Tumor development implies PI3K/AKT pathway activation. Akt isoforms (1,2,3) 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. Objective: Identification of Akt isoforms activated in sevoflurane exposed breast tumor cells. Material and methods: Normal breast cells MCF10A (ATCC®) and breast cancer cells MDA-MB-231 (ATCC®) were cultured 2D (standard adhesive culture plastic plates) and 3D (matrigel). Study groups were exposed to different sevoflurane concentrations (0.5, 2, 3, 4 mM) compared to control unexposed groups. Unexposed and sevoflurane exposed cells (2D and 3D) were evaluated by optic microscopy and viability tests. Akt isoforms were assessed by immunofluorescence. Results: Sevoflurane alters tumor cell proliferation and Akt isoforms expression in a dose-dependent manner. The phenotype of 3D 2mM sevoflurane exposed cells show an increased migration capacity which indicates increased aggressivity. Conclusions: Sevoflurane exposure of breast cancer cells influences cell proliferation, phenotype and Akt isoform expression. Increased sevoflurane concentrations activate different Akt isoforms, putatively related to epithelial-mesenchimal transition and promote cancer cell invasion, migration and metastasis.