Propofol inhibits Wnt signaling and exerts anticancer activity in glioma cells

丙泊酚抑制 Wnt 信号并在胶质瘤细胞中发挥抗癌活性

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

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 in vivo. 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.

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