Takahiro Hirai1, Yuko Konishi2, Shoko Mizuno3, Zhou Rui1, Yao Sun1, Kimitoshi Nishiwaki1. 1. Department of Anesthesiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. 2. Endowed Division of Perioperative Management, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. ykonishi@med.nagoya-u.ac.jp. 3. Aichi Spine Institute, 31-1, Kamiike, Goromaru, Inuyama, Aichi, 484-0066, Japan.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Thomas Kuilman; Chrysiis Michaloglou; Liesbeth C W Vredeveld; Sirith Douma; Remco van Doorn; Christophe J Desmet; Lucien A Aarden; Wolter J Mooi; Daniel S Peeper Journal: Cell Date: 2008-06-13 Impact factor: 41.582