The effect of aflibercept and arsenic trioxide on the proliferation, migration and apoptosis of oral squamous cell carcinoma in vitro

Mol Biol Rep. 2021 Apr;48(4):3223-3235. doi: 10.1007/s11033-021-06341-w. Epub 2021 Apr 30.

Abstract

Aflibercept and arsenic trioxide drugs apply a cytotoxic effect on some human cancer cell lines. However, no more study has followed the effects of both drugs, especially arsenic trioxide, on oral squamous cell carcinoma (OCC). We used three OCC lines as a model to show the effect of these drugs on the genetically complex disease and investigate its targeted therapy. In this study, three human OCC cell lines were used from different patients. We treated cell lines with both medications to detect the effect and relevant molecular basis. First, methyl thiazolyl tetrazolium (MTT) assay was performed to detect the cytotoxicity effect and cell growth. Second, flow cytometry, gene and protein expression were performed to evaluate the anti-angiogenic effect on OCC lines. Next apoptosis was analyzed by flow cytometry. Finally, clonogenesis capacity and cell migration were assessed by colony formation assay and wound healing, respectively. Aflibercept had no cytotoxic effect on the three OCC cell lines but decreased cell growth rate. Arsenic trioxide had a significant cytotoxic effect on three cell lines. Our results demonstrated that both drugs significantly decreased endoglin, VEGFA, and VEGFB expression. In addition, Migration and colony formation assays confirmed that these drugs have significant anti-proliferative and anti-migration effect on oral carcinoma cells. These results revealed that both medications might be a potential drug for the management of oral cancer patients.

Keywords: Aflibercept; Arsenic trioxide; OCC; Oral squamous cell carcinoma.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Arsenic Trioxide* / pharmacology
  • Arsenic Trioxide* / toxicity
  • Carcinoma, Squamous Cell* / drug therapy
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Endoglin / drug effects
  • Endoglin / metabolism
  • Humans
  • Mouth Neoplasms* / drug therapy
  • Receptors, Vascular Endothelial Growth Factor*
  • Recombinant Fusion Proteins* / pharmacology
  • Recombinant Fusion Proteins* / toxicity
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Vascular Endothelial Growth Factor A / drug effects
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor B / drug effects
  • Vascular Endothelial Growth Factor B / metabolism

Substances

  • Antineoplastic Agents
  • Endoglin
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor B
  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor
  • Arsenic Trioxide