PTEN Is Activated by the Addition of Cetuximab to Paclitaxel in Oral Squamous Cell Carcinoma

Anticancer Res. 2021 Jul;41(7):3363-3370. doi: 10.21873/anticanres.15124.

Abstract

Background/aim: The mechanisms through which cetuximab (cMab) coadministration with paclitaxel (PTX) enhances antitumor efficacy remain unclear. We examined the mechanism of the antitumor enhancing effect of cMab by determining changes in gene expression in the PI3K-AKT pathway.

Materials and methods: Eight human oral squamous cell carcinoma (OSCC) cell lines were cultured three-dimensionally and exposed to PTX + cMab. The expression levels of PTEN mRNA in OSCC cell lines after anticancer drug treatment were assessed using real-time PCR. PTEN mRNA expression levels were also confirmed after administration of PTX + cMab in vivo. Western blot analysis was used to confirm the results at the protein level.

Results: PTEN mRNA and protein expression were significantly increased only in the cell lines with high sensitivity to PTX + cMab, and similar results were observed in vivo.

Conclusion: PTEN activation may enhance the antitumor effect of PTX + cMab.

Keywords: Anticancer drug sensitivity test; CD-DST; PTEN; cetuximab; paclitaxel.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cetuximab / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / genetics*
  • PTEN Phosphohydrolase / genetics*
  • Paclitaxel / pharmacology
  • Phosphatidylinositol 3-Kinases / genetics
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / genetics*

Substances

  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Paclitaxel
  • Cetuximab