Volatile anaesthetics enhance the metastasis related cellular signalling including CXCR2 of ovarian cancer cells.
Volatile anaesthetics enhance the metastasis related cellular signalling including CXCR2 of ovarian cancer cells.
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DOI：
10.18632/oncotarget.8304
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Ma D
中科院分区：
文献类型：
--
作者：
Iwasaki M;Zhao H;Jaffer T;Unwith S;Benzonana L;Lian Q;Sakamoto A;Ma D
大多数卵巢癌患者在手术切除后复发。越来越多的证据表明手术在癌细胞扩散中的作用；特别是麻醉可能对癌症的复发有影响。在这里，我们研究了挥发性麻醉剂异氟醚、七氟醚和地氟醚对卵巢癌细胞的转移潜力。人卵巢癌细胞（SKOV3）分别暴露于异氟烷（2%）、七氟烷（3.6%）和地氟烷（10.3%）中2小时。使用肿瘤转移PCR阵列和qRT-PCR检测转移相关基因表达谱。随后采用免疫荧光染色法检测血管内皮生长因子A （VEGF-A）、基质金属蛋白酶11 （MMP11）、转化生长因子β -1 （TGF-β1）和趋化因子（C-X-C基序）受体2 （CXCR2）蛋白的表达。通过划痕实验评估SK-OV3细胞的迁移能力，并通过siRNA敲低CXCR2进一步研究CXCR2在介导挥发性麻醉药对癌细胞生物学影响中的潜在作用。所有三种挥发性麻醉剂均改变了81个转移相关基因中的70个的表达，其中VEGF-A、MMP-11、CXCR2和TGF-β基因和蛋白表达显著增加，其数量级为地氟烷（最大）、七氟烷和异氟烷。划痕分析显示，暴露于这些麻醉剂会增加迁移，而这种迁移被CXCR2敲除所消除。临床相关浓度的挥发性麻醉剂对癌细胞生物学有很强的影响，进而可能增加卵巢癌的转移潜力。这项工作提出了进一步的体内研究和临床试验的紧迫性，然后才能在临床实践的改变方面做出任何结论。
The majority of ovarian cancer patients relapse after surgical resection. Evidence is accumulating regarding the role of surgery in disseminating cancer cells; in particular anaesthesia may have an impact on cancer re-occurrence. Here, we have investigated the metastatic potential of volatile anaesthetics isoflurane, sevoflurane and desflurane on ovarian cancer cells. Human ovarian carcinoma cells (SKOV3) were exposed to isoflurane (2%), sevoflurane (3.6%) or desflurane (10.3%) for 2 hours. Metastatic related gene expression profiles were measured using the Tumour Metastasis PCR Array and qRT-PCR. Subsequently vascular endothelial growth factor A (VEGF-A), matrix metalloproteinase 11 (MMP11), transforming growth factor beta-1 (TGF-β1) and chemokine (C-X-C motif) receptor 2 (CXCR2) proteins expression were determined using immunofluorescent staining. The migratory capacities of SK-OV3 cells were assessed with a scratch assay and the potential role of CXCR2 in mediating the effects of volatile anaesthetics on cancer cell biology were further investigated with CXCR2 knockdown by siRNA. All three volatile anaesthetics altered expression of 70 out of 81 metastasic related genes with significant increases in VEGF-A, MMP-11, CXCR2 and TGF-β genes and protein expression with a magnitude order of desflurane (greatest), sevoflurane and isoflurane. Scratch analysis revealed that exposure to these anesthetics increased migration, which was abolished by CXCR2 knockdown. Volatile anaesthetics at clinically relevant concentrations have strong effects on cancer cell biology which in turn could enhance ovarian cancer metastatic potential. This work raises the urgency for further in vivo studies and clinical trials before any conclusions can be made in term of the alteration of clinical practice.
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