Liu Qiuyue, Li Ru, Lin Jun
Department of Anesthesiology, Stony Brook University School of Medicine, Stony Brook, NY, United States.
Currently Department of Intensive Care Unit, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical University, Beijing, China.
Front Pharmacol. 2022 Feb 9;13:794109. doi: 10.3389/fphar.2022.794109. eCollection 2022.
This study evaluates the effect of the commonly used inhaled anesthetics isoflurane, sevoflurane, and desflurane on the viability and migration of murine 4T1 breast cancer cells, the growth, and lung metastasis in a syngenetic model of spontaneous metastasis. The murine 4T1 breast cancer cells were exposed to isoflurane (2%), sevoflurane (3.6%), or desflurane (10.3%) for 3 h. Cell viability was measured using the MTT assay. The migratory capacity of 4T1 cells was assessed using a scratch assay after 24 h incubation. Female balb/c mice were subjected to orthotopic implantation of 4T1 cells under anesthesia with one of the inhaled anesthetics: 2% isoflurane, 3.6% sevoflurane, or 10.3% desflurane. Subsequently, resection of primary tumors was performed under the identical anesthetic used during implantation for 3 h. Three weeks later, the mice were euthanized to harvest lungs for bioluminescent imaging and histological analysis. Blood was collected for serum cytokine assays by ELISA. There was no difference in cell viability among isoflurane, sevoflurane, desflurane, and control groups ( = 180 for each group, = 0.648). Sevoflurane but not isoflurane or desflurane significantly increased the migration of 4T1 cells compared to the control group ( = 18, = 0.024). There was no difference in the growth of the orthotopically implanted primary tumors ( = 12 for the isoflurane group, = 11 for the sevoflurane group, and for the desflurane group, = 0.879). Surgical dissection of primary tumors in mice under anesthesia with isoflurane, sevoflurane, or desflurane led to no difference in lung metastasis following surgery ( = 0.789). No significant difference was observed among isoflurane, sevoflurane, and desflurane groups in the serum levels of IL-6 ( = 0.284), CCL-1 ( = 0.591), MCP-1 ( = 0.135), and VEGF ( = 0.354). Our study demonstrated that sevoflurane increased the migration of 4T1 breast cancer cells . Inhaled anesthetics isoflurane, sevoflurane, and desflurane had no difference on the growth of primary tumor and the lung metastasis of 4T1 cells in the mouse model of spontaneous metastasis with surgical removal of primary tumors.
本研究评估了常用吸入麻醉药异氟烷、七氟烷和地氟烷对小鼠4T1乳腺癌细胞活力和迁移能力的影响,以及在自发转移的同基因模型中对肿瘤生长和肺转移的影响。将小鼠4T1乳腺癌细胞分别暴露于2%异氟烷、3.6%七氟烷或10.3%地氟烷中3小时。使用MTT法测量细胞活力。孵育24小时后,使用划痕试验评估4T1细胞的迁移能力。雌性balb/c小鼠在吸入麻醉药(2%异氟烷、3.6%七氟烷或10.3%地氟烷)麻醉下进行4T1细胞原位植入。随后,在植入时使用的相同麻醉下进行原发性肿瘤切除,持续3小时。三周后,对小鼠实施安乐死以获取肺部进行生物发光成像和组织学分析。通过ELISA收集血液用于血清细胞因子检测。异氟烷、七氟烷、地氟烷组与对照组之间的细胞活力无差异(每组n = 180,P = 0.648)。与对照组相比,七氟烷可显著增加4T1细胞迁移能力(n = 18,P = 0.024),而异氟烷和地氟烷则无此作用。原位植入的原发性肿瘤生长情况无差异(异氟烷组n = 12,七氟烷组n = 11,地氟烷组n = 11,P = 0.879)。在异氟烷、七氟烷或地氟烷麻醉下对小鼠原发性肿瘤进行手术切除后,肺转移情况无差异(P = 0.789)。异氟烷、七氟烷和地氟烷组之间,血清IL-6(P = 0.284)、CCL-1(P = 0.591)、MCP-1(P = 0.135)和VEGF(P = 0.354)水平无显著差异。我们的研究表明,七氟烷可增加4T1乳腺癌细胞的迁移能力。在原发性肿瘤手术切除的自发转移小鼠模型中,吸入麻醉药异氟烷、七氟烷和地氟烷对4T1细胞原发性肿瘤生长和肺转移无差异影响。