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The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence
Cell Biology and Toxicology ( IF 6.1 ) Pub Date : 2022-08-12 , DOI: 10.1007/s10565-022-09747-9
Masae Iwasaki 1, 2 , Hailin Zhao 1 , Cong Hu 1 , Junichi Saito 1, 3 , Lingzhi Wu 1 , Aislinn Sherwin 4 , Masashi Ishikawa 1, 2 , Atsuhiro Sakamoto 2 , Donal Buggy 4 , Daqing Ma 1
Affiliation  

Anaesthetics may modify colorectal cancer cell biology which potentially affects long-term survival. This study aims to compare propofol and sevoflurane regarding with the direct anaesthetic effects on cancer malignancy and the indirect effects on host immunity in a cancer xenograft mode of mice. Cultured colon cancer cell (Caco-2) was injected subcutaneously to nude mice (day 1). Mice were exposed to either 1.5% sevoflurane for 1.5 h or propofol (20 μg g−1; ip injection) with or without 4 μg g−1 lipopolysaccharide (LPS; ip) from days 15 to 17, compared with those without anaesthetic exposure as controls. The clinical endpoints including tumour volumes over 70 mm3 were closely monitored up to day 28. Tumour samples from the other cohorts were collected on day 18 for PCR array, qRT-PCR, western blotting and immunofluorescent assessment. Propofol treatment reduced tumour size (mean ± SD; 23.0 ± 6.2mm3) when compared to sevoflurane (36.0 ± 0.3mm3) (p = 0.008) or control (23.6 ± 4.7mm3). Propofol decreased hypoxia inducible factor 1α (HIF1α), interleukin 1β (IL1β), and hepatocyte growth factor (HGF) gene expressions and increased tissue inhibitor of metalloproteinases 2 (TIMP-2) gene and protein expression in comparison to sevoflurane in the tumour tissue. LPS suppressed tumour growth in any conditions whilst increased TIMP-2 and anti-cancer neutrophil marker expressions and decreased macrophage marker expressions compared to those in the LPS-untreated groups. Our data indicated that sevoflurane increased cancer development when compared with propofol in vivo under non-surgical condition. Anaesthetics tested in this study did not alter the effects of LPS as an immune modulator in changing immunocyte phenotype and suppressing cancer development.



中文翻译:

小鼠癌症异种移植模型中与麻醉相关的差异性癌症生长:术后癌症复发的机制和影响

麻醉剂可能会改变结直肠癌细胞的生物学特性,从而可能影响长期生存。本研究旨在比较异丙酚和七氟醚对癌症恶性肿瘤的直接麻醉作用以及在小鼠癌症异种移植模型中对宿主免疫的间接影响。将培养的结肠癌细胞(Caco-2)皮下注射到裸鼠(第1天)。从第15天到第17天,小鼠暴露于1.5%七氟烷1.5小时或异丙酚(20 μg g -1;腹腔注射),有或没有4 μg g -1脂多糖(LPS;腹腔注射),与没有暴露麻醉剂的小鼠相比控制。临床终点(包括肿瘤体积超过 70 mm 3 )在第 28 天之前均受到密切监测。在第 18 天收集其他队列的肿瘤样本用于 PCR 阵列、qRT-PCR、蛋白质印迹和免疫荧光评估。与七氟烷 (36.0 ± 0.3mm 3 ) (p = 0.008) 或对照 (23.6 ± 4.7mm 3 ) 相比,异丙酚治疗减小 了肿瘤大小(平均值 ± SD;23.0 ± 6.2mm 3 )。与七氟醚相比,异丙酚降低肿瘤组织中缺氧诱导因子 1α (HIF1α)、白细胞介素 1β (IL1β) 和肝细胞生长因子 (HGF) 基因表达,并增加金属蛋白酶组织抑制剂 2 (TIMP-2) 基因和蛋白质表达。与 LPS 未治疗组相比,LPS 在任何条件下都能抑制肿瘤生长,同时增加 TIMP-2 和抗癌中性粒细胞标记物的表达,并减少巨噬细胞标记物的表达。我们的数据表明,在非手术条件下,与异丙酚相比,七氟醚在体内会增加癌症的发展。本研究中测试的麻醉剂并没有改变脂多糖作为免疫调节剂在改变免疫细胞表型和抑制癌症发展方面的作用。

更新日期:2022-08-12
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