Hirai Takahiro, Konishi Yuko, Mizuno Shoko, Rui Zhou, Sun Yao, Nishiwaki Kimitoshi
Department of Anesthesiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
Endowed Division of Perioperative Management, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
J Anesth. 2020 Feb;34(1):47-57. doi: 10.1007/s00540-019-02701-w. Epub 2019 Oct 31.
There have been contradictory findings regarding the effects of sevoflurane on the oncogenic properties of cancer cells. This study was conducted to gain insights into the fundamental rules governing the differential effects of sevoflurane exposure on various cancer cells derived from multiple origins.
A series of cancer cell lines were exposed to 1% (v/v) sevoflurane for 2-8 h and then assessed for their proliferation, Matrigel invasion, and apoptotic cell death, in comparison with their untreated counterparts. Cell proliferation and Matrigel invasion assays were performed using Coulter counter and Boyden chamber techniques, respectively. Apoptosis was evaluated by staining cells with Annexin V and 7-AAD followed by fluorescence flow cytometry. In addition, the expression of cleaved caspase-3 protein, another marker of apoptosis, was assessed using immunoblotting.
Proliferation was significantly enhanced after sevoflurane exposure in six of eight cancer cell lines (NCI-H1299, MDA-MB-231, HCT116, DLD-1, HT29, and RKO). In contrast, sevoflurane attenuated proliferation in the last two cancer cell lines, A549 and MCF-7, as well as in the non-cancerous MCF10A cell line. Cell biological assays using four cancer cell lines demonstrated that accelerated but not attenuated cancer cell proliferation after sevoflurane exposure is associated with enhanced Matrigel invasion and suppressed apoptosis.
Sevoflurane augmented or hampered cell proliferation and Matrigel invasion depending on the cancer cell line examined. Loss of sevoflurane-induced apoptosis occurring in cancer cell lines is likely to be correlated with their enhanced proliferation after sevoflurane exposure.
关于七氟醚对癌细胞致癌特性的影响,存在相互矛盾的研究结果。本研究旨在深入了解七氟醚暴露对多种来源的不同癌细胞产生差异影响的基本规律。
将一系列癌细胞系暴露于1%(v/v)七氟醚中2 - 8小时,然后与未处理的对应细胞系相比,评估其增殖、基质胶侵袭和凋亡性细胞死亡情况。分别使用库尔特计数器和博伊登小室技术进行细胞增殖和基质胶侵袭试验。通过用膜联蛋白V和7 - 氨基放线菌素D对细胞进行染色,随后进行荧光流式细胞术来评估凋亡情况。此外,使用免疫印迹法评估凋亡的另一个标志物——裂解的半胱天冬酶 - 3蛋白的表达。
在八个癌细胞系中的六个(NCI - H1299、MDA - MB - 231、HCT116、DLD - 1、HT29和RKO)中,七氟醚暴露后增殖显著增强。相比之下,七氟醚使最后两个癌细胞系A549和MCF - 7以及非癌性MCF10A细胞系的增殖减弱。使用四个癌细胞系进行的细胞生物学试验表明,七氟醚暴露后癌细胞增殖加速而非减弱与基质胶侵袭增强和凋亡受抑制有关。
七氟醚增强或阻碍细胞增殖和基质胶侵袭,这取决于所检测的癌细胞系。癌细胞系中七氟醚诱导的凋亡缺失可能与其在七氟醚暴露后增殖增强相关。