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实体肿瘤手术切除以后可能发生转移，而转移是癌症致死的主要原因。不过，手术麻醉药对癌症转移的影响及其具体机制尚不明确。 2020年1月31日，英国《自然》旗下《自然通讯》发表美国纽约州立石溪大学的研究报告，探讨了手术麻醉药对乳腺癌肺转移的影响及其潜在机制。 该研究利用同基因小鼠三阴性乳腺癌细胞4T1和人类乳腺癌胸膜转移细胞MDA-MB-231异种移植模型，对全身吸入麻醉药七氟烷与全身静脉麻醉药丙泊酚进行比较，结果发现七氟烷与丙泊酚相比，小鼠原发肿瘤切除后肺转移的比例显著较高。 根据机制分析，七氟烷可以增加血清白细胞介素IL-6的水平，从而激活信号转导及转录激活蛋白STAT3，促进整联蛋白CD11b阳性髓样细胞向肺的浸润。 对于三阴性乳腺癌细胞4T1模型，JAK激酶抑制剂AZD1480可以阻断IL-6→JAK→STAT3通路，逆转七氟烷激活STAT3和CD11b阳性细胞浸润的促转移作用。 因此，该临床前研究结果表明，可以通过全身靶向治疗改变细胞因子和肿瘤微环境，从而改变麻醉药对乳腺癌转移的特殊影响。 Nat Commun. 2020 Jan 31;11(1):642. Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models. Li R, Huang Y, Lin J. Stony Brook University, Stony Brook, NY, USA. Metastasis can occur following surgical resection of solid tumors and metastasis is the main cause of cancer death. The role of anesthetics used during surgery in cancer metastasis and the underlying mechanism remains largely unknown. Here we show that surgical dissection of primary tumors in mice under anesthesia with sevoflurane leads to significantly more lung metastasis than with propofol in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. Sevoflurane increases the level of serum IL-6, which activates STAT3 and the infiltration of CD11b+ myeloid cells into the lung. Interruption of IL-6/JAK/STAT3 pathway by a JAK inhibitor AZD1480 reverses the pro-metastatic effect of sevoflurane and the associated increase of both activated STAT3 and infiltrated CD11b+ cells in 4T1 model. Our study provides the preclinical evidence informing the distinct effects of anesthetics on metastasis of breast cancers through change of cytokines and the tumor microenvironment. PMID: 32005799 DOI: 10.1038/s41467-019-14065-6
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