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丙泊酚抑制Wnt信号传导并在胶质瘤细胞中发挥抗癌活性。

Propofol inhibits Wnt signaling and exerts anticancer activity in glioma cells.

作者信息

Xu Wei, Zheng Jiwei, Bie Shijie, Kang Liuyu, Mao Qingjun, Liu Weiwei, Guo Jinxin, Lu Juan, Xia Rui

机构信息

Department of Anesthesiology, The First People's Hospital of Jingzhou, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China.

Operating Room, The First People's Hospital of Jingzhou, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434000, P.R. China.

出版信息

Oncol Lett. 2018 Jul;16(1):402-408. doi: 10.3892/ol.2018.8606. Epub 2018 May 2.

Abstract

Aberrant activation of Wnt signaling is implicated in gliomagenesis. Propofol, the most commonly used intravenous anesthetic agent in clinics, exhibits potent antitumor activity in a variety of cancer cells through different mechanisms. However, the role of propofol on Wnt signaling and glioma cell growth remains to be fully elucidated. In the present study, propofol was identified as a potent inhibitor of Wnt signaling. In 293T cells transfected with Wnt1 or Wnt3 expression plasmids or treated with Wnt3A-conditioned medium, propofol significantly inhibited the transcriptional activity of the SuperTopFlash reporter and the expression of Wnt target genes. The inhibitory effect of propofol on Wnt signaling was also observed in glioma cells. Further experiments demonstrated that propofol suppressed glioma cell growth by decreasing cell proliferation and enhancing cell apoptosis. Finally, the potential antitumor efficiency of propofol was confirmed using xenograft experiments . Taken together, the results indicated a novel mechanism for the anticancer activity of propofol and provide supporting evidence for its use as a prospective anticancer drug to treat glioma in patients with deregulated Wnt signaling.

摘要

Wnt信号通路的异常激活与胶质瘤的发生有关。丙泊酚是临床上最常用的静脉麻醉剂,通过不同机制在多种癌细胞中表现出强大的抗肿瘤活性。然而,丙泊酚对Wnt信号通路和胶质瘤细胞生长的作用仍有待充分阐明。在本研究中,丙泊酚被确定为Wnt信号通路的有效抑制剂。在转染了Wnt1或Wnt3表达质粒或用Wnt3A条件培养基处理的293T细胞中,丙泊酚显著抑制了SuperTopFlash报告基因的转录活性和Wnt靶基因的表达。在胶质瘤细胞中也观察到了丙泊酚对Wnt信号通路的抑制作用。进一步的实验表明,丙泊酚通过减少细胞增殖和增强细胞凋亡来抑制胶质瘤细胞生长。最后,通过异种移植实验证实了丙泊酚潜在的抗肿瘤效果。综上所述,这些结果揭示了丙泊酚抗癌活性的新机制,并为其作为一种有望治疗Wnt信号通路失调患者胶质瘤的抗癌药物提供了支持证据。

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