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The anti-tumor effect of regorafenib in lung squamous cell carcinoma in vitro

Xiu Hu1, Lin-Wen Wu1, Zuo-Yan Zhang1

  • 1School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang, 310015, China; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, China.

Biochemical and Biophysical Research Communications
|June 27, 2018
PubMed

Insights

Regorafenib effectively inhibits lung squamous cell carcinoma (LSCC) proliferation by inducing cell cycle arrest. Activating glycogen synthase kinase 3 beta (GSK3β) hinders this anti-cancer effect, suggesting GSK3β as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Lung squamous cell carcinoma (LSCC) is a subtype of non-small-cell lung cancer (NSCLC) with limited effective treatment options.
  • Regorafenib, an oral multikinase inhibitor, has shown potential anti-tumor activity in various solid tumors.

Purpose of the Study:

  • To investigate the anti-proliferative effects of regorafenib on LSCC cell lines.
  • To explore the underlying mechanisms, including the role of glycogen synthase kinase 3 beta (GSK3β).

Main Methods:

  • Treatment of LSCC cell lines with regorafenib.
  • Analysis of cell proliferation and cell cycle progression (G0/G1 arrest).
  • Assessment of GSK3β protein levels and phosphorylation status (Ser9).

Main Results:

  • Regorafenib demonstrated significant anti-proliferative effects on LSCC cells by inducing G0/G1 cell cycle arrest.
  • GSK3β levels remained stable, but its Ser9 phosphorylation decreased with increasing regorafenib exposure.
  • Inhibition of GSK3β activity potentiated the anti-tumor effects of regorafenib.

Conclusions:

  • Regorafenib exhibits promising therapeutic potential for LSCC.
  • GSK3β activation appears to restrict regorafenib's anti-cancer efficacy in LSCC.
  • Targeting GSK3β may enhance the anti-tumor activity of regorafenib in LSCC treatment.
Keywords:
Cell proliferationDrug resistanceGSK3βLung squamous cell carcinomaRegorafenib

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