2. Academic Validation
  3. Propofol inhibits invasion and proliferation of C6 glioma cells by regulating the Ca2+ permeable AMPA receptor-system xc- pathway

Propofol inhibits invasion and proliferation of C6 glioma cells by regulating the Ca2+ permeable AMPA receptor-system xc- pathway

  • Toxicol In Vitro. 2017 Oct;44:57-65. doi: 10.1016/j.tiv.2017.06.026.
Xin-Yue Wang 1,  Yan-Li Li 2,  Hai-Yun Wang 3,  Min Zhu 4,  Di Guo 1,  Guo-Lin Wang 5,  Ying-Tang Gao 6,  Zhuo Yang 7,  Tang Li 1,  Chen-Yi Yang 1,  Yi-Meng Chen 1
Affiliations

Affiliations

  • 1 Department of Anesthesiology, the Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Tianjin Institute of Hepatobiliary Disease, Artificial Cell Engineering Research Centre of the Ministry of Health, Tianjin 300170, China.
  • 2 Department of Cardiology, Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Tianjin Institute of Hepatobiliary Disease, Artificial Cell Engineering Research Centre of the Ministry of Health, Tianjin 300170, China.
  • 3 Department of Anesthesiology, the Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Tianjin Institute of Hepatobiliary Disease, Artificial Cell Engineering Research Centre of the Ministry of Health, Tianjin 300170, China; Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: why819@126.com.
  • 4 Department of Anesthesiology, Tianjin first Central Hospital, Tianjin 300192, China.
  • 5 Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 6 Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cell, Tianjin Institute of Hepatobiliary Disease, Artificial Cell Engineering Research Centre of the Ministry of Health, Tianjin 300170, China.
  • 7 College of Medicine, Nankai University, Tianjin 300071, China.
PMID: 28663055 DOI: 10.1016/j.tiv.2017.06.026
Abstract

Anesthetics are documented to affect tumors; therefore, we studied the antiglioma effect of propofol on proliferation and invasiveness of glioma cells and explored the underlying mechanism. C6 glioma cells were cultured and treated with propofol, and cell viability, invasiveness, and migration were measured. Glutamate release was measured using an enzyme-catalyzed kinetic reaction. xCT protein and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR2 subunit protein expression was assessed with Western blot analysis and immunofluorescent staining. We observed that propofol significantly inhibited C6 glioma cell viability, invasiveness, and migration and decreased glutamate release. An agonist of the cystine/glutamate antiporter system (system xc-), N-acetylcysteine (NAC), reversed propofol's effects, and propofol could inhibit C6 glioma cell proliferation by adding excess exogenous glutamate (100μM). Finally, propofol increased the surface expression of GluR2, but decreased surface expression of xCT. The effects of propofol on surface expression of GluR2 and xCT could be rescued by (R, S)-AMPA, an agonist of CA2+ permeable AMPA Receptor (CPAR). Thus, propofol can inhibit cell viability, invasiveness, and migration of C6 glioma cells, and the CPAR-system xc- pathway contributes to these events.

Keywords

Amino acid transport system; C6 glioma cell; Ca(2+) permeable AMPA receptor; Propofol.

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