Abstract 2162: Comparing volatile and intravenous anesthetics in a mouse model of breast cancer metastasis
Authors: Li Ru , Huang Yujie , Liu Hengrui , Dilger James P. , Lin Jun 
Published: August 2018

Abstract
Introduction: Retrospective studies have suggested that anesthesia maintained with intravenous propofol during oncological surgery is associated with better outcome than anesthesia with volatile anesthetics. Here, we determine the effects of anesthetics on breast cancer lung metastasis in an animal model.
Methods: A primary tumor is generated in 6-8 week old Balb/c female mice by orthotopic implantation of 4T1 mouse breast cancer cells expressing firefly luciferase, into the mammary gland. When the primary tumor volume reaches 500 mm3, it is resected under three-hour anesthesia either with 2.7% inhaled sevoflurane or a 150 mg/kg intraperitoneal injection of propofol. A control group does not receive surgery or anesthesia. After surgery, lung metastasis is tracked and quantified with noninvasive bioluminescent imaging (IVIS). Two weeks later, the mice are euthanized, and the lungs are harvested for macroscopic and histological analyses, which include counting metastatic nodules, and CD11b/CD31 overlay staining.
As a step towards understanding the mechanism, we examine the effect of propofol and sevoflurane on angiogenesis. An in vivo matrigel plug assay is used to evaluate the effect of anesthetics on blood vessel formation. Balb/c mice are administered 2.7% sevoflurane or 150 mg/kg propofol 1 hour each week for three weeks. A control group receives no anesthetic. Blood vessels are visualized by perfusion of TRITC labeled dextran. No surgery is done in this experiment.
Results: In the 4T1 syngeneic model, surgical resection of the primary tumor under propofol anesthesia significantly reduced spontaneous lung metastasis in comparison with sevoflurane. Using IVIS imaging, similar levels of bioluminescence in the lung were observed in control and propofol treated mice two weeks after surgery. In contrast, mice anesthetized with sevoflurane had 1.5-fold higher levels (p&lt;0.0001). This was consistent with manual counts of tumor nodules on the lungs: the number of tumor nodules increased by more than 300% in sevoflurane group versus control or propofol group (p&lt;0.0001). The in vivo matrigel plug assay showed that exposure of Balb/c mice to sevoflurane led to a 2-fold increase in blood vessel density over control (no anesthesia). Propofol decreased blood vessel density.
Conclusion: We used a mouse model to recapitulate the human clinical situation in which the choice of anesthestic given during cancer surgery may be a risk factor for cancer metastasis. Our results show that the volatile anesthetic sevoflurane preferentially promotes metastasis of breast cancer cells in the lung. This may be related to the ability of sevoflurane to promote angiogenesis. The 4T1 mouse model successfully recapitulated the differential effects of anesthetic agents on breast cancer development seen in clinic, and further deepen our understanding of the mechanism behind that phenomenon.
Citation Format: Ru Li, Yujie Huang, Hengrui Liu, James P. Dilger, Jun Lin. Comparing volatile and intravenous anesthetics in a mouse model of breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2162.