Sevoflurane modulates breast cancer cell survival via modulation of intracellular calcium homeostasis

BMC Anesthesiology

Divakara Gouda¹  Huafeng Wei¹  Ge Liang¹  Xiaoqian Deng²  Beibei Wang³  Megha Vipani⁴ 

[1] Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, 305 John Morgan Building, 3610 Hamilton Walk, 19104, Philadelphia, PA, USA;Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, 305 John Morgan Building, 3610 Hamilton Walk, 19104, Philadelphia, PA, USA;Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China;Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, 305 John Morgan Building, 3610 Hamilton Walk, 19104, Philadelphia, PA, USA;Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong Science and Technology University, Wuhan, China;Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, 305 John Morgan Building, 3610 Hamilton Walk, 19104, Philadelphia, PA, USA;University of Virginia School of Medicine, 22903, Charlottesville, VA, USA;

关键词: Anesthetics;    Breast;    Cancer;    Survival;    Metastasis;    Ca;    TRP Channel;   

DOI  :  10.1186/s12871-020-01139-y

来源: Springer

【 摘 要 】

BackgroundSome retrospective and in vitro studies suggest that general anesthetics influence breast cancer recurrence and metastasis. We compared the effects of general anesthetics sevoflurane versus propofol on breast cancer cell survival, proliferation and invasion in vitro. The investigation focused on effects in intracellular Ca2+ homeostasis as a mechanism for general anesthetic-mediated effects on breast cancer cell survival and metastasis.MethodsEstrogen receptor-positive (MCF7) and estrogen receptor-negative (MDA-MB-436) human breast cancer cell lines along with normal breast tissue (MCF10A) were used. Cells were exposed to sevoflurane or propofol at clinically relevant and extreme doses and durations for dose- and time-dependence studies. Cell survival, proliferation and migration following anesthetic exposure were assessed. Intracellular and extracellular Ca2+ concentrations were modulated using Ca2+ chelation and a TRPV1 Ca2+ channel antagonist to examine the role of Ca2+ in mediating anesthetic effects.ResultsSevoflurane affected breast cancer cell survival in dose-, time- and cell type-dependent manners. Sevoflurane, but not propofol, at equipotent and clinically relevant doses (2% vs. 2 μM) for 6 h significantly promoted breast cell survival in all three types of cells. Paradoxically, extreme exposure to sevoflurane (4%, 24 h) decreased survival in all three cell lines. Chelation of cytosolic Ca2+ dramatically decreased cell survival in both breast cancer lines but not control cells. Inhibition of TRPV1 receptors significantly reduced cell survival in all cell types, an effect that was partially reversed by equipotent sevoflurane but not propofol. Six-hour exposure to sevoflurane or propofol did not affect cell proliferation, metastasis or TRPV1 protein expression in any type of cell.ConclusionSevoflurane, but not propofol, at clinically relevant concentrations and durations, increased survival of breast cancer cells in vitro but had no effect on cell proliferation, migration or TRPV1 expression. Breast cancer cells require higher cytoplasmic Ca2+ levels for survival than normal breast tissue. Sevoflurane affects breast cancer cell survival via modulation of intracellular Ca2+ homeostasis.

【 授权许可】

CC BY